RU2714882C2 - Pharmaceutical dosage form for use on mucous membranes - Google Patents

Abstract

FIELD: medicine; pharmaceuticals.SUBSTANCE: present invention relates to a pharmaceutical dosage form for use on a mucosa of the esophagus, nasopharyngeal, buccal, gastrointestinal, rectal or vaginal mucosa. Dosage form contains at least one platy preparation containing an active pharmaceutical ingredient, a release mechanism and a trigger mechanism capable of triggering release by the platy preparation release mechanism in a preset exposure point of the gastrointestinal tract, rectum or vagina. Pharmaceutical dosage form also comprises a shell containing said platy preparation containing an active pharmaceutical ingredient, wherein the shell has at least one opening through which the liquid surrounding the shell can come into contact with the inner space of the shell, where the opening is made in the form of a slot and/or at least partially coated with a trigger mechanism, or the platy preparation is folded into grooves or recesses of dosage form, wherein the folds are glued together by a polymer triggering the release of the pharmaceutical ingredient. Release mechanism represents a mechanism of expansion that leads to opening of shell, or opening forms part of release mechanism and is configured to release the preparation from the shell so that the platy preparation is untwisted or straightened when the dosage form moves along the mucous membrane and leaves the shell through the opening.EFFECT: dosage form according to the invention provides release of the active pharmaceutical ingredient in the increased volume and in the preset exposure point.20 cl, 8 dwg, 2 tbl, 7 ex

Description

FIELD OF THE INVENTION

The present invention relates to a dosage form for use on mucous membranes, in particular buccal, intestinal, rectal or vaginal mucous membranes.

State of the art

The dosage form is designed to contain at least one lamellar preparation, in particular a film-like, foil or wafer containing the active pharmaceutical ingredient, its release mechanism and the trigger mechanism, and the trigger mechanism is configured to trigger the release of the lamellar drug by the release mechanism in a given place exposure, in particular in the gastrointestinal tract, rectum or vagina.

Due to this, among other things, an advantage is provided in increasing the bioavailability of the active pharmaceutical ingredient by pressing a film-like, foil or cachet preparation to the mucous membrane at the site of application, providing controlled contact, rapid absorption of the drug through the mucous membrane into the blood, and thereby increasing bioavailability.

First of all, bioavailability is a measure of pharmacological effects, which is of great importance for the applicability of the active pharmaceutical ingredient and the dosage form containing such an ingredient. As a rule, bioavailability indicates how quickly and to what extent the active pharmaceutical ingredient is absorbed and, accordingly, reabsorbed and available at the site of exposure. For intravenous drugs, bioavailability is by definition 100%.

The bioavailability observed after oral administration is commonly referred to as oral bioavailability.

Many drugs are not particularly suitable for oral administration because they exhibit too low bioavailability and / or highly variable intraindividual plasma concentrations. Possible reasons for this are deterioration or inactivation of the active substance due to the secretion of digestive juices and enzymes, the diluting effect of intestinal fluids, low absorbability, high presystem metabolism and a short stay on the suction surface. Such drugs include, for example, proteins and peptides, such as insulin, buserelin, desmopressin, calcitonin and estrogen, as well as drugs obtained by biotechnological methods, such as antibodies, for example, rituximab.

Numerous attempts are known to investigate various mucous membranes of mammals, in particular humans, and to improve the bioavailability of active pharmaceutical ingredients. Particular attention in such studies is given to the properties of various mucous membranes of mammals, in particular humans, regarding the permeability for absorption of the drug and its effect.

Studies suggest that mucosal permeability relative to various drugs increases in the following order: intestinal mucosa <colon mucosa <buccal mucosa - vaginal mucosa (Alam, MA et al., "Everted gut sac model as a tool in pharmaceutical research: limitations and applications ", Journal of Pharmacy and Pharmacology, 2011, Vol. 64, pages 326-336; Berginc, K. et al.," Development and Evaluation of an In Vitro Vaginal Model for Assessment of Drug's Biopharmaceutical Properties: Curcumin ", AAPS PharmSciTech, Vol. 13, No. 4, 2012, pages 1045-1053; van der Biji, P. et al.," Comparative in vitro permeability of human vaginal, small intestinal and colonic mucosa. "International Journal of Pharmaceutics, 2003, Vol. 261, pages 147-152; van der Biji, P. et al.," Penetration of human vaginal and buccal mucosa by 4.4-d and 12-kd fluorescein -isothiocyanatelabeled dextrans ", Oral surgery oral medicine oral pathology, 1998, Vol. 85, No. 6, pages 686-691; Hosoya, K. et al., "The Structural Barrier of absorptive Mucosae: Site Difference of the Permeability of Fluorescein labeled Dextran in Rabbits", Biopharmaceutics & Drug Disposition, 1993, Vol. 14, pages 685-696).

In addition, research results show that the use of a high concentration active pharmaceutical ingredient directly on the mucous membranes can increase its bioavailability compared to a solution or tablet (Gupta, V. et al. "Mucoadhesive intestinal devices for oral delivery of salmon calcitonin". Journal of Controlled Release, 2013, Vol. 172, Issue 3, pages 753-762; Teutonico, D. et al. "Concentration and surface of absorption: Concepts and applications to gastrointestinal patch delivery". International Journal of Pharmaceutics, 2011, Vol 413, pages 87-92).

Such concentrated use of the active pharmaceutical ingredient directly on the mucous membranes can be carried out using dosage forms containing the active pharmaceutical ingredient in the form of a plate, in particular film, foil preparation or in the form of a cachet, in particular in the form of the so-called wafer cachet. A disadvantage of traditional wafers is, in particular, that known wafers are dissolved partially or completely until they reach the point of exposure, and in relation, for example, intestinal, rectal or vaginal wafers, the absence of contact with the mucous membrane will be guaranteed. Moreover, with respect to, for example, intestinal, rectal or vaginal multilayer wafer wafers, contact with the right side of the wafer and, especially, sufficiently long contact with the mucous membrane cannot be guaranteed.

An object of the present invention is to provide a pharmaceutical dosage form in which the aforementioned disadvantages are eliminated.

Another objective of the present invention is the development of a pharmaceutical dosage form, which increases the bioavailability of the active pharmaceutical ingredients that are contained in dosage forms, administered, in particular, by the oral, vaginal or rectal route.

Another objective of the present invention is the development of a pharmaceutical dosage form, in particular, a dosage form containing the active pharmaceutical ingredient in the form of a plate, in particular a film, foil or wrapping preparation, preferably in the form of a cachet, in which the release of the active pharmaceutical ingredient is achieved in a predetermined site of exposure, the amount of active pharmaceutical ingredient available for absorption is increased and / or increased bioavailable five and / or increased degree of suction.

Including, the aim of the present invention is to develop a dosage form of rapid release with a systemic effect. Finally, another objective of the invention is to develop a dosage form that allows the use of active pharmaceutical ingredients that, due to low bioavailability, cannot be administered orally at a predetermined site of exposure.

In particular, the present invention relates to pharmaceutical dosage forms for administration mainly in the upper parts of the gastrointestinal tract, such as the pharynx, esophagus, cardia and / or stomach, in particular, in the corresponding mucous membranes, which allows for local drug therapy and / or diagnostic examination. Local diseases, in particular, diseases of the esophagus, can be treated with topical drugs. However, as a rule, existing pharmaceutical dosage forms or systems of administration are often not focused on a specific focus of the disease; in particular, they are not oriented to the esophagus and / or the mucosa of the esophagus. As a result of this, as a rule, most of the administered drug, in particular the active pharmaceutical ingredient, is absorbed somatically, which can cause side effects, in particular undesirable reactions. In particular, in connection with the foregoing, one of the objectives of the present invention is to increase the effectiveness of topical application of a medicinal product, in particular, an active pharmaceutical ingredient. Preferably, specific embodiments of the present invention mainly achieve and / or only aim to achieve this objective of the present invention. Moreover, in some embodiments, the present invention can provide additional tasks. Among other things, certain embodiments of the present invention may have the goal of increasing the bioavailability of the active pharmaceutical ingredient, the local delivery of a beneficial substance, mainly a drug, such as an active pharmaceutical ingredient, treating the esophagus with a topical drug and / or reducing side effects, in particular adverse reactions. Disclosure of Invention

These and other tasks can be solved using the objects of the independent claims. Special cases of the embodiment of the invention are set forth in the dependent claims.

In particular, the authors of the present invention take advantage of varying degrees of permeability of various mucous membranes and especially their ability to absorb various drugs, which, among other things, differ in their molecular size and lipophilicity, to create a dosage form that will allow direct contact of the dosage form with mucous membrane after release at a predetermined site of exposure.

In particular, the present invention is a pharmaceutical dosage form for use on mucous membranes, in particular on buccal, intestinal, rectal or vaginal mucous membranes, which includes at least one lamellar, in particular film, foil or wrapping preparation, comprising an active pharmaceutical ingredient, a release mechanism, and a trigger mechanism, wherein the trigger mechanism is configured to trigger release of the plate drug tween the drug release mechanism in a predetermined position of the impact, located in particular in the gastrointestinal tract, the rectum or vagina.

Such a pharmaceutical dosage form according to the invention has advantages, since it allows to increase the bioavailability of active pharmaceutical ingredients, which, in particular, are contained in drugs administered orally, vaginally or rectally, at a predetermined site of exposure. Additionally, by using the pharmaceutical dosage form of the invention, the release of the active pharmaceutical ingredient at a predetermined site of exposure can be achieved, whereby, in particular, the amount of active pharmaceutical ingredient available for absorption can be increased, and the bioavailability and degree of absorption can also be increased.

In particular, this can be achieved using the dosage form according to the invention due to the fact that the dosage form according to the invention quickly releases a lamellar, in particular a film, foil or wrapping preparation containing the active pharmaceutical ingredient, at a predetermined site of exposure. Among other things, the dosage form of the present invention allows the use of active pharmaceutical ingredients that cannot be administered orally due to low bioavailability at a predetermined site of exposure.

A preferred predetermined site of exposure may be the mucosa, in particular the buccal, intestinal, rectal or vaginal mucosa.

The pharmaceutical dosage form according to the invention, thereby, makes it possible to establish contact, in particular direct contact, at a predetermined site of action, in particular with the mucous membrane, preferably with tissue absorbing the active pharmaceutical ingredient, and subsequently introduce the drug into the blood, which is an advantage. An embodiment of the preparation containing the active pharmaceutical ingredient is a lamellar, in particular a film, foil or wraparound preparation, in particular the so-called wafer wafer, allows you to release the lamellar preparation directly on the mucous membrane and establish contact with it, preferably contact with a relatively large surface area, at a predetermined site of exposure, after which the lamellar preparation can dissolve and release active pharmaceutical dients. Such contact at a predetermined site of exposure has advantages, since it allows to increase the absorption of the active pharmaceutical ingredient, in particular, in the mucous membrane, as a result of which the amount of active pharmaceutical ingredient available for absorption increases. Bioavailability and / or degree of absorption therefore also increase.

Intestinal presystemic metabolism, i.e. the conversion of the active pharmaceutical ingredient during its first passage through the intestinal mucosa and, optionally, through the liver, in particular from the oral dosage form, can be reduced by using the pharmaceutical dosage form of the present invention. In addition, the disintegration of the active pharmaceutical ingredient before it reaches a predetermined site of exposure, for example, by the action of gastric acid and / or digestive enzymes, can be significantly reduced using the pharmaceutical dosage form of the present invention. The bioavailability of the active pharmaceutical ingredient is also advantageously increased by the pharmaceutical dosage form of the present invention. The pharmaceutical dosage form of the present invention, in particular, allows to reduce the dose, providing approximately equivalent therapeutic effect, especially compared with the use of similar traditional drugs, such as tablets, solutions, vaginal creams or suppositories. Moreover, the pharmaceutical dosage form of the present invention allows more accurate dosage of the active pharmaceutical ingredient, and also, if necessary, reduce side effects, in particular side effects from the gastrointestinal tract. The pharmaceutical dosage form of the present invention also provides relatively simple and clear handling, as well as simple, in particular compact, storage in which the active pharmaceutical ingredients that contain the pharmaceutical dosage form of the present invention can have increased stability, for example, under high temperature and humidity, in particular, in comparison with solutions and gels.

The combination of a plate preparation containing the active pharmaceutical ingredient with a trigger mechanism and a release mechanism, implemented according to the present invention, with great advantage retains the positive characteristics of the plate preparation, in particular, wafer wafers.

At a predetermined trigger location, which may or may not coincide with the site of exposure, the trigger mechanism triggers, for example, under the action of a key stimulus, the release mechanism and, therefore, the release of the plate preparation at the site of exposure. For example, the release mechanism begins to open and release the lamellar preparation from the shell after the trigger mechanism triggers the release mechanism, for example, by contact with a key stimulus, for example, depending on a change in pH, a change in pressure, or a change in fluid.

It should be understood that the terms "place of exposure" and "place of application" used in the present description are interchangeable. In this regard, it should also be understood that the "place of exposure" and "place of application" refer to a predetermined place of release of the drug. It should also be understood that the active pharmaceutical ingredient that is released at the “site of exposure” or at the “site of use” may also have an actual effect on another part of the body or on another part of the biochemical cycle, for example, during or after metabolization by the liver or upon reaching antibody of its target molecule. The terms "place of exposure" and "place of use" used in the present description do not necessarily refer to the place of biochemical, therapeutic action of the active pharmaceutical ingredient.

The pharmaceutical dosage form of the present invention, in particular, allows you to protect the plate preparation, in particular, the wafer, until the drug reaches a predetermined point of exposure or place of use, and bring the plate preparation, in particular, the wafer, into contact with a predetermined place exposure, in particular with the mucous membrane.

The pharmaceutical dosage form of the present invention, thus, provides directional and complete adhesion to a predetermined site of exposure or place of use.

Also, among other things, this allows prolonging the residence time on the suction surface, displacing liquids, which can lead to premature separation or dissolution of the plate preparation, in particular, wafer wafers.

In a preferred embodiment, the pharmaceutical dosage form according to the invention, the pharmaceutical dosage form, among other things, has a shell that contains at least one lamellar, in particular film, foil or wrapping, a preparation containing the active pharmaceutical ingredient, and the shell or trigger mechanism preferably contain at least one hole through which the fluid surrounding the shell can come into contact with the interior of the shell, where the hole ochtitelno designed as slots and / or at least partially covered by a trigger mechanism.

In particular, the coating of the preparation protects the preparation against unwanted release.

It should be understood that the pharmaceutical dosage form according to the invention may have a shell, which contains at least one or more plate preparations containing the active pharmaceutical ingredient. The shell of the pharmaceutical dosage form according to the invention and / or the dosage form itself also contains a release mechanism and / or a trigger mechanism, wherein the trigger mechanism is configured to trigger the release of the plate preparation by the release mechanism at a predetermined site of exposure, in particular, in the gastrointestinal tract.

The release of the plate preparation by the release mechanism preferably occurs by at least partially leaving the preparation from at least a portion of the shell.

The hole in the shell provides a particularly advantageous way of contacting the fluid surrounding the shell, in particular the fluid at a predetermined starting point, for example, fluid of the gastrointestinal tract, into the interior of the shell and / or contact of the fluid with the interior of the shell, in particular trigger mechanism and / or release mechanism, which are located in the inner space of the shell.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the opening is in the form of a slot.

Such a slot can be made in various layouts and configurations. For example, such a slot may be located wholly or partially around the circumference of the shell. The slot, which is located completely around the entire circumference of the shell, can be located so that it divides the shell into several parts, in particular into two parts.

The hole of the present invention, in particular a slot, can also be positioned so that when the plate preparation is released from the shell, the plate preparation exits through the hole, in particular through the slot. In a preferred embodiment of the pharmaceutical dosage form of the present invention, the opening may be coated with a trigger mechanism, at least partially or completely.

Preferably, the trigger mechanism covers the hole at least partially or completely, thereby allowing, in particular, to regulate, in particular, to avoid undesired penetration of the surrounding liquid into the envelope.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the trigger mechanism is configured to trigger the release of the plate preparation by the release mechanism after the pharmaceutical dosage form, in particular, the trigger mechanism, is exposed to a key stimulus.

The term “key stimulus”, as used herein, preferably refers to a change in the environmental state of the pharmaceutical dosage form of the present invention, which is sufficient to trigger the trigger mechanism. Such a change in the state of the environment, which is sufficient to actuate the trigger mechanism, is preferably a change that characteristically occurs at a predetermined site of exposure, for example, in the gastrointestinal tract. Such a change in the state of the environment may be a predetermined change in the physical or chemical environmental parameter of the dosage form. For example, at a predetermined site of exposure, preferably in the gastrointestinal tract, the pressure or pH characteristic of the predefined site of exposure, or the composition of the environment, for example, a liquid medium at the site of exposure, specific to the predefined site of exposure, and, in particular, changing these parameters can serve as a key stimulus. For example, a significantly lower pH in the stomach compared to the usual pH in the cervical region, in the oral cavity and pharynx, and in particular, a change in pH from the cervical region, oral cavity, and pharyngeal cavity to the stomach can serve as a key stimulus.

In particular, the fluid surrounding the dosage form at a predetermined site of exposure, for example, gastric juice and / or other fluid of the gastrointestinal tract, or vaginal fluid at a predetermined site of exposure, may include a predetermined pH, a predetermined pressure, or a predetermined composition, or a change in these parameters, which is enough to actuate the trigger mechanism.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the trigger mechanism is configured to trigger release of the plate preparation by the release mechanism in a time-controlled manner or immediately, and / or the trigger mechanism is configured to release the plate preparation in a time-controlled manner or immediately after the trigger is triggered. mechanism.

It should be understood that a key stimulus that is suitable for actuating the trigger mechanism at a predetermined trigger location can trigger the trigger mechanism immediately or with a delay, in particular in a time-controlled manner, so that the trigger mechanism is configured to release the plate preparation using the release mechanism immediately or with a delay, so that the release occurs at a predetermined site of exposure, in particular in the gastrointestinal tract, in the vagina or in ryamoy intestine. The release mechanism can also be designed in such a way as to release the lamellar preparation immediately or with a delay, in particular, in a time-controlled manner, at a predetermined point of exposure after the trigger mechanism is activated.

In a particular preferred embodiment of the pharmaceutical dosage form of the present invention, the trigger mechanism is configured to trigger release of the plate preparation by the release mechanism immediately and / or relatively quickly, and / or the release mechanism is configured to release the plate preparation immediately and / or relatively quickly after being triggered trigger mechanism.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the key incentive for actuating the trigger mechanism involves the presence of a predetermined change in the physical or chemical parameter of the fluid surrounding the dosage form, in particular at a predetermined launch site, preferably at a predetermined location of the gastrointestinal tract, rectum or vagina, and the key stimulus is mainly selected from the group consisting of a predetermined change pH, a predetermined change in pressure or a predetermined change in the composition of the liquid surrounding the dosage form.

A key stimulus can be chosen in such a way that it acts on the trigger mechanism immediately at a predetermined location of exposure or even before reaching a predetermined location of exposure at a predetermined trigger location, which differs from the location of exposure. A key stimulus can trigger the trigger mechanism immediately or with a delay, it can, in particular, trigger the trigger mechanism in a time-controlled manner. The release of the release mechanism can occur immediately or with a delay, in particular, in a time-controlled manner, after the trigger mechanism is actuated. In particular, the actuation of the trigger mechanism with a delay, in particular, the time-controlled actuation of the trigger mechanism, can be carried out already when the dosage form is removed from the package during oral, rectal or vaginal administration, when it enters a predetermined section of the gastrointestinal a tract, in particular, a section of the rectum or a section of the vagina, or when leaving it, when a predetermined temperature, pH of the environment, or in the presence or absence of specific substances in the environment surrounding the dosage form. Alternatively, the actuation of the trigger mechanism when the dosage form is orally administered, when it enters a predetermined section of the gastrointestinal tract, in particular, the rectum or vagina, or when exited when a predetermined temperature or environmental pH is reached, or in the presence or absence of specific substances in the environment surrounding the dosage form, it can cause an immediate and / or relatively quick actuation of the trigger mechanism.

Immediate and / or relatively quick actuation of the trigger mechanism and / or immediate and / or relatively quick release of the release mechanism may give the advantage of bringing the plate preparation into contact with the site of exposure, in particular the mucous membrane, in contact with the relatively a large surface area and / or in providing a significantly larger surface area for absorption of the active pharmaceutical ingredient at the site of exposure.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the trigger mechanism comprises a substance whose solubility and strength depend on at least the physical and / or chemical parameter of the liquid surrounding the dosage form, preferably selected from the group consisting of pH, pressure or composition of the liquid, surrounding dosage form.

Preferably, the trigger mechanism is configured such that its physical and chemical properties, for example, its configuration and / or state of aggregation, are altered by a key stimulus as described herein, whereby the trigger mechanism can trigger the release of the plate preparation by the release mechanism in a predetermined exposure site. Changes in the properties of the trigger mechanism can occur immediately or with a delay, in particular, in a time-controlled manner, or dynamically after exposure to a key stimulus at a predetermined trigger location.

Changing the properties of the trigger mechanism can trigger an immediate or delayed, in particular, time-controlled or dynamic, release of the plate preparation at the site of exposure. The term "dynamic" used in the present description, it should preferably be understood that there is a corresponding reaction to conditions existing at the launch site and at the site of exposure, for example, in the gastrointestinal tract. In other words, this applies, for example, to the principle that the intestinal contents remain acidic, whereby the trigger mechanism is not (yet) activated, and as a result, the release mechanism does not release.

The term "time-controlled", as used herein, refers preferably to a predetermined time. For example, release occurs after a predetermined period in the case of a time-controlled release.

It is also contemplated within the scope of the present invention that the release of the release mechanism occurs immediately after the actuation of the trigger mechanism. Alternatively, the release of the release mechanism can occur with a delay that can be set or that can dynamically change after the trigger mechanism is activated.

A change in the properties of the trigger mechanism can be caused by swelling, dissolution, or a change in the strength of the trigger mechanism or part thereof.

In this context, it should be understood that the trigger mechanism immediately or with a delay, in particular, adjustable in time or dynamic, for example, after a predetermined period of time, triggers the release of the lamellar preparation by the release mechanism after exposure to a key stimulus. For example, the trigger mechanism can unlock the mobility of other elements, for example, a release mechanism, dosage form or holes that regulate the flow of fluid surrounding the membrane into the interior of the membrane, such as the fluid of the gastrointestinal tract or vagina, as a result of exposure to a key stimulus.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the trigger mechanism is a layer that at least partially covers the hole and / or release mechanism, or part thereof.

In particular, in a preferred embodiment of the pharmaceutical dosage form of the present invention, the dosage form is a tampon for vaginal use, the tampon being at least partially wrapped, coated and / or filled with a lamellar, in particular film, foil or wrapping preparation containing active pharmaceutical ingredient. This tampon can successfully serve as a trigger mechanism and, for example, swell upon contact with the vaginal fluid as a key stimulus, and can also trigger, due to the increase in the circumference or diameter of the tampon, the release of the lamellar preparation due to the release mechanism. In particular, such a release can establish the contact of a lamellar, in particular film, foil or cachet preparation containing the active pharmaceutical ingredient, with a predetermined site of action, in particular, with the vaginal mucosa, while the laminar preparation abuts against the vaginal mucosa. Additionally or alternatively, such a tampon dosage form may be at least partially coated with a (additional) trigger mechanism and / or shell, in particular in the form of a layer.

In particular, the trigger mechanism, which covers the hole and / or the release mechanism, or at least partially or completely, can be placed and / or configured to loosen, dissolve or swell the trigger mechanism after exposure to a key stimulus, whereby the trigger mechanism is preferably triggers the release of a plate preparation.

In particular, the hole, or slot, can be hermetically closed or covered with a trigger mechanism, made in the form of a coating, so that the penetration of liquid into the dosage form, preferably into the interior of the shell, is excluded, while such a trigger mechanism can dissolve under the influence of the key stimulus at a predetermined trigger site and / or may erupt as a result of the release of the plate preparation at a predetermined site of exposure. With regard to mechanical properties, such a coating is preferably made in such a way that it does not dissolve in the fluids surrounding the dosage form, for example, vaginal fluids or fluids of the gastrointestinal tract, and thus retains its strength and integrity. It is generally recognized that it is advisable to create a coating so that the release mechanism can generate sufficient force so that the coating is torn at the time of release. If the coating dissolved before release, i.e. before the release mechanism develops sufficient force, for example, due to swelling or gas formation, to release the drug, the fluid surrounding the dosage form, in particular in the form of a capsule, could fill the form and create an obstacle to the drug. In particular, with regard to the release mechanism, which is mechanically pre-stressed, whereby it can develop a force at any time, such a coating can be soluble, whereby at the same time it can serve as a trigger mechanism.

The trigger mechanism, which at least partially closes or covers the hole or slot, may contain a substance whose solubility depends on the key stimulus, in particular, on the pH value of the environment. For example, the trigger mechanism may be at least partially made of a substance that is predominantly selected from a soluble polymer, hydroxypropyl methylcellulose phthalate or eudragit.

It should be understood that, in particular, a predetermined site of exposure, in particular, the release site of the plate preparation, can be determined based on a pH-dependent change in the solubility of the trigger mechanism and / or substance that is contained in the trigger mechanism.

In addition, in the framework of the present invention is also considered limiting the mobility of one or more elements of the dosage form, in particular, the release mechanism, relative to each other, in particular due to the trigger mechanism, for example, so that they remain fixed in the initial position, and which, in particular, the release mechanism, remains fixed in its initial position until the trigger mechanism starts.

It should be understood that after removal of mobility restrictions, in particular, after a change in the property and / or conformational change, in particular, a change in the solubility of the trigger mechanism, the location and / or properties of one or more elements of the dosage form, in particular, the release mechanism, change relative to each other each other so that the release mechanism can be triggered and the plate preparation can be released using the release mechanism.

In this case, the release of the lamellar preparation may affect the release mechanism by changing the property and / or conformational change, in particular, changing the solubility, directly the release mechanism and / or the key stimulus, which is similar or different from the key stimulus that triggers the trigger mechanism, directly or with using intermediate elements that are selected from the group consisting of, for example, rods, levers, springs, traction and pushing devices, or the like in.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the dosage form, in particular the shell and / or trigger mechanism, contains at least one predetermined break point.

The term “predetermined break point” as used herein preferably means a notch and / or perforation, preferably a notch that changes its strength and other properties under the influence of a certain pressure.

Such a predetermined rupture site may be part of a shell, in particular a dosage form capsule, part of a release mechanism, or part of a trigger mechanism.

In particular, such a predetermined gap, preferably a gap formed in the form of a notch on the material, may consist of the same or another material from which the element containing the gap is made. For example, a shell made of hard gelatin may have a predetermined break point, which is also formed by hard gelatin, in particular, a shell made of hard gelatin may have a predetermined break point in the form of a notch on hard gelatin.

A person skilled in the art is able to determine the properties of a predetermined gap in relation to the present invention, in particular the properties associated with the gap, taking into account the origin and composition of the material, geometric shape or other parameters related to strength.

For example, a predetermined rupture site related to the present invention can be made and / or arranged so that after exposure to a predetermined pressure on a dosage form, in particular a predetermined rupture site, it ruptures and unlocks the mobility of other elements of the dosage form, in particular, the release mechanism and / or the trigger mechanism, in particular, the holes that regulate the flow of gastrointestinal fluid into the dosage form.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell is formed from a material that is practically insoluble in a liquid present at a predetermined launch site and / or at a predetermined site of exposure, in particular in the gastrointestinal tract. However, it should be understood that such a shell may be insoluble not only in a predetermined launch site, but also in other departments through which it is necessary to pass in order to reach the place of onset of action and / or the site of exposure, i.e. all the way to a predetermined place.

In a preferred embodiment of the present invention, the membrane consists or mainly consists of a material that is practically insoluble in the fluid present at a predetermined launch site and / or at a predetermined site of exposure, in particular in the fluid of the rectum, vagina or gastrointestinal a path, mainly in vaginal fluid or in gastric juice.

A material that is practically insoluble in vaginal fluid or gastric juice is preferably selected from the group consisting of gastric juice resistant polymers containing acidic polymethacrylates, such as copolymers of methacrylic acid and methyl methacrylate 1: 1 (Eudragit L), copolymers of methacrylic acid and methyl methacrylate 1: 2 (Eudragit L), a copolymer of methacrylic acid and ethyl acrylate 1: 1 (Eudragit L 100-5 5), acidic cellulose derivatives such as hydroxypropyl methylcellulose acetate succinates (HPMCAS) type -LF, -MF and / il and -HF and cellulose acetate phthalate; vinyl alcohol-based acid polymers such as polyvinyl acetate and vinyl acetate: crotonic acid copolymer; Zein, keratin, gluten, shellac, gelatin and alginic acid, fortified with formaldehyde or glutaraldehyde.

In this context, it should be understood that the trigger mechanism, in particular when it is made as covering the hole, is preferably made of a material that is different from the material of the shell, in particular, of a material that is practically insoluble in the liquid present in a predetermined launch site and / or at a predetermined site of exposure, in particular in the rectum, vagina or gastrointestinal tract, preferably in vaginal fluid or in gastric juice.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell is made of a material selected from the group consisting of hard gelatin, polymers, thermoplastics, such as, for example, eudragit or the like. In this regard, in particular, it is advisable to use those materials that have already been successfully tested, used and / or approved for use, for example, for oral dosage forms.

In another preferred embodiment, the pharmaceutical dosage form of the present invention, the shell consists of a material that is selected from the group consisting of hard gelatin and polymers.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell is capsule-shaped.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell is made of a material that is practically insoluble in the liquid present at a predetermined launch site or at the site of exposure, in particular in the gastrointestinal tract, preferably insoluble in the gastric juice, wherein the shell preferably consists of a material selected from the group consisting of polymers and / or hard gelatin.

Preferably, such substantially insoluble material, in particular practically insoluble in vaginal fluid or in gastric juice, is selected from the group consisting of gastric juice resistant polymers containing acidic polymethacrylates, such as 1: 1 methacrylic acid / methyl methacrylate copolymers (Eudragit L ), copolymers of methacrylic acid and methyl methacrylate 1: 2 (Eudragit L), a copolymer of methacrylic acid and ethyl acrylate 1: 1 (Eudragit L 100-5 5), copolymers of ammonium methacrylate (for example, Eudragit RS), acidic derivatives nye celluloses such as hydroxypropyl methylcellulose acetate succinates (GPMTSAS) type -LF, -MF and / or -HF and cellulose acetate phthalate; vinyl alcohol-based acid polymers such as polyvinyl acetate and vinyl acetate: a cretonic acid copolymer; Zein, keratin, gluten, shellac, gelatin and alginic acid, fortified with formaldehyde or glutaraldehyde. In particular, an ammonium methacrylate copolymer is a material for the shell and / or trigger mechanism.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the dosage form, in particular the shell and / or trigger mechanism, comprises a wick system, in particular a capillary system, which is adapted to direct liquid into the dosage form using capillary forces.

Such a wick system with great advantage allows you to perform preferably a predetermined or controlled introduction of fluid from the fabric, in particular by means of capillary forces, into the dosage form, in particular, into the inner space of the shell, due to the capillary action of the wick system.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the dosage form, in particular the shell and / or trigger mechanism, comprise a wick system.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the release mechanism, or part thereof, is an expansion mechanism or comprises such an expansion mechanism.

The term "expansion mechanism", as used herein, preferably refers to a release mechanism of a plate preparation that is configured such that the plate preparation can be expanded to a predetermined volume, i.e. after activating the release mechanism, the plate preparation increases to its predetermined volume or expands to a predetermined volume, respectively. For example, a plate preparation, in particular, a wafer wafer, can be enclosed in a shell having smaller spatial parameters, for example, it can be crumpled, compressed, folded or reduced to a smaller format in another way. A release mechanism comprising an expansion mechanism, or an expansion mechanism that is implemented as a release mechanism or as part of it, is preferably configured to expand or expand a plate preparation, which can be enclosed in a shell with a smaller spatial size, to a predetermined size after activating the release mechanism in particular, to distribute, open or unfold the plate preparation, or to bring it to a larger size in another way.

This provides an advantageous opportunity to create a relatively small dosage form, in particular for rectal, oral or vaginal administration, in which the surface area of the plate preparation can in particular be increased by expanding the plate preparation, in particular to release the active ingredient in a predetermined place of exposure. In addition, the contact surface of a predetermined site of exposure, in particular of the vagina, rectum or gastrointestinal tract, for example, the surface of the mucous membrane or wall of the intestine that comes into contact with the flat preparation, can also be enlarged.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the expansion mechanism is selected from the group consisting of a mechanical expansion system, a gas expansion system, compressed foam, or compressed fabric.

In one embodiment of the present invention, the expansion mechanism is a gas system. Such a gas expansion system may comprise a high pressure vessel, which may be filled with a gas generating agent.

Advantageously, the gas generated by the gas generating agent can affect the expansion of the plate preparation.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the release mechanism, in particular the expansion mechanism, comprises a blowing agent, which is preferably selected from the group consisting of sodium bicarbonate and citric acid.

In one embodiment of the present invention, the expansion system is a mechanical system. Such a mechanical system can be implemented as a connecting or lever expander. In particular, such a mechanical system can be designed such that the shell contains at least one connecting or lever element, which is preferably located at the free end of the shell.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the expansion mechanism is configured such that at least partial opening of the membrane occurs as a result of its expansion.

This at least partial opening of the shell allows you to release the lamellar preparation at a predetermined site of exposure, in particular in the vagina, in the rectum or in the gastrointestinal tract.

In a preferred embodiment, the pharmaceutical dosage form of the present invention, the dosage form contains the drug in folded form, and the expansion mechanism is designed so that its expansion leads to the deployment of the drug.

Preferably, the unfolding of the preparation may also lead to the opening of the shell, in particular the capsule.

This advantageously allows you to create a relatively small dosage form in which the surface area of the plate preparation can be increased by unfolding it, in particular, to release the active ingredient at a predetermined site of exposure, for example, on the mucous membrane.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell, preferably the wick system, if present, contains a blowing agent as a release mechanism, in particular as an expansion mechanism, and the blowing agent is selected from the group consisting of sodium bicarbonate, citric acid , sodium dihydrogen phosphate, compressed gas, liquefied gas and boiling liquid.

It should be understood that after the opening of the hole with the trigger mechanism, the wick system preferably directs the fluid surrounding the dosage form at a predetermined site of exposure, in particular, in the rectum, vagina or gastrointestinal tract, to a gassing substance, which then due to a chemical reaction forms a gas, for example, carbon dioxide, which expands and accordingly fills a gas-resistant shell, which can be filled with gas, in particular a cylinder.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the preparation is in the form of a gas-tight shell, in particular a cylinder that can be filled with gas, and / or the dosage form contains a folded preparation, preferably made in the form of a gas-tight shell, which can be filled gas, in particular in the form of a cylinder.

It should be understood that such a drug, made in the form of a gas-resistant shell, which can be filled with gas, can be expanded, preferably by means of an expansion mechanism, in particular by a gas expansion system, and can be released at a predetermined site of exposure, in particular in a predetermined location of the gastrointestinal tract. In a particularly advantageous embodiment, the gas-tight shell, in particular, the cylinder, which can be filled with gas, can be expanded, in particular, filled, by introducing gas into it. The pressure resulting from this within the gas-filled shell, in particular the balloon, preferably leads to close contact of its external surface with a predetermined site of exposure, in particular, with the mucous membrane or with the intestinal wall. In addition, advantageously, the mucous membrane or wall of the intestine or a portion of the mucous membrane or wall of the intestine can be slightly stretched so as to increase the available surface area for absorption of the active pharmaceutical ingredient, which is an advantage.

In an alternative embodiment of the pharmaceutical dosage form of the present invention, a gas-filled gas-tight shell, in particular a cylinder, and / or a dosage form, contains a gas-tight, gas-filled shell in a folded form, while the gas-filled shell, in particular the balloon, is coated with a plate preparation .

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the gas generating agent is located in a portion of a shell that is preferably opposite to a portion of the shell containing the drug and / or which is preferably facing the shell portion of the drug.

Moreover, the shell can be at least partially incised in that part which is opposite to the part of the shell containing the drug and / or which faces the portion of the shell containing the drug, so that preferably the shell can be opened by a gas-filled shell, in particular , balloon, when expanded by filling with gas, so that the membrane can enter, for example, into the lumen of the rectum, vagina or gastrointestinal tract.

It should be understood that with this configuration, the shell can be partially opened in such a slot, preferably due to the pressure created by the introduced gas, and the shell, which can be filled with gas, in particular a balloon, can be released.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the dosage form comprises a preparation, preferably in the form of a gas-filled gas-tight shell, in particular in the form of a balloon, the gas-tight shell containing a hole that is circumferentially attached to the inner boundary of the shell.

Preferably, the boundary of such a hole is located on the inner boundary of the shell, so that gas from the inner space of the shell can rush into a gas-resistant shell, which can be filled with gas, in particular a balloon.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell is divided along the outer contour.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell, in particular the expansion mechanism, preferably a mechanical expansion system, comprises at least a first connecting or lever element, preferably a hinge. Such a connecting or lever element, in particular the first connecting or lever element, is preferably arranged so that the shell, preferably the shell, is divided along the contour, in particular when it consists of several parts that are pivotally connected to such a connecting or lever element, can open wide or open. Such a connecting or lever element, in particular, a first connecting or lever element, can advantageously be in the form of a mechanical hinge, in the form of paper and / or due to added materials with elastic properties. In particular, such a connecting or lever element may be integral with the shell or may be attached to it (for example, glued).

The plate dosage form, in particular the wafer, can be folded in the interior of the shell and can be attached to the shell, in particular to one edge or several edges of the shell (preferably composite), opposite the first connecting or lever element, in particular hinged so that the rotation or opening, tilting or swinging of the shell or part of the shell with the first connecting or lever element expands, in particular, unfolds and / or ra kryvalo platelet dosage form.

To facilitate such expansion, in particular the deployment of the plate preparation as a dosage form, the dosage form may contain additional elements.

In particular, such additional elements can be arranged so as to advantageously increase the angle of inclination, which increases the release of the plate preparation. For this purpose, the shell may contain one or more additional connecting or lever elements or flexible parts in addition to the first connecting or lever element. In this context, it should be understood that the connecting or lever elements can be made with the possibility of disclosure of the drug. Additionally or alternatively, additional elements may be configured to perform only this task. In addition, parts of the composite shell can perform this task. In other words, in order to disclose the preparation and / or dosage form, in particular to obtain a “tent-like” structure, for example, rods and arcs can be provided. Additionally or alternatively, sponges or similar elements can also advantageously be used to open the dosage form, however, they cannot promote expansion or can only slightly expand. Moreover, lever systems can be created in order to implement a kind of transmission stage, which translates the slight movement of the release mechanism into the intense movement of the entire dosage form.

In an embodiment with a shell that is contoured and / or contains a slot, it is possible to advantageously avoid unwanted penetration into the shell of the liquid surrounding the shell and / or dosage form, in particular penetration into the intermediate space between the two edges of the shell if the slot and / or a slot located at the edges of two sides of the shell, which is divided at least partially along the contour, is covered with a sealing layer. In particular, the sealing layer may be made of a flexible material, for example, waxed or adhesive. In particular, it is advisable that possible unevenness at the edges of the shell will be compensated in this way. Alternatively or additionally, a slot and / or a slot at the edges of the two parts of the shell, which is divided along the contour, can also be covered with a sealing layer to prevent unwanted penetration of the surrounding liquid into the shell. In addition, alternatively or additionally, a slot and / or a slot along the edges of two parts of the shell, which is divided along the contour, can be fully or partially covered with a sealed coating, in particular, on the inner and / or outer wall of the shell, and / or can be covered at least partially by a trigger mechanism.

In this context, it is also contemplated within the framework of the present invention that the slot and / or slot at the edges of two parts of the shell, which is divided along the contour, can be a hole in the shell and / or trigger mechanism in accordance with various embodiments of the present invention.

It is also contemplated within the scope of the present invention that the sealing layer and / or the trigger mechanism can be broken down after opening the shell, in particular after clicking on the shell, or with the possibility of preliminary dissolution.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell, in particular the expansion mechanism, preferably a mechanical expansion system, comprises at least one spring element.

For example, such a spring element may be configured to open the shell, in particular by clicking the opening of the shell. To this end, the spring element can be made in the form of a prestressed spring element, in particular, a prestressed spring, which applies the compression force of the spring to the shell or its part, where the compression force of the spring is sufficient to open the shell by clicking. A sealing layer or trigger mechanism can counteract this opening of the shell by clicking or opening the shell with a spring. After dissolution and / or destruction of the sealing layer and / or the trigger mechanism, the opening of the shell may occur, in particular, click opening by a spring. Additionally or alternatively, additional elements can also be provided that transmit the movement of the spring, for example, this function can also be performed, in accordance with the present description, by a hinge, lever or connecting element.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the preparation comprises a swelling agent, wherein the swelling agent is preferably selected from the group consisting of sponge and fibers.

Preferably, the swelling aid is located in or in part of the shell. After the triggering mechanism is activated, the swelling agent can be positioned so that the release of the drug, in particular unfolding, takes place at a predetermined site of exposure, in particular in the gastrointestinal tract, and / or in such a way that the drug can be applied to a predetermined site of exposure, for example, on the mucous membrane or on the wall of the intestine. In this regard, it is preferable that the substance that promotes swelling, was part of the release mechanism or itself was a release mechanism, in particular, an expansion mechanism. Preferably, the swelling aid is a sponge or contains fibers, in particular compressed layers of fibers that preferably contain cellulose and / or consist of other suitable swellable material.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell comprises at least a first tubular element and optionally at least one additional tubular element.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell comprises a first tubular element and at least a second tubular element, where the second tubular element has a smaller tube diameter than the first tubular element.

Preferably, the sheath is formed by at least a first and / or at least one first and at least one additional tubular element.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell comprises a first tubular element and at least a second tubular element, where the second tubular element has a smaller tube diameter than the first tubular element, and where the second tubular element is at least partially located in the first tubular element or inserted into the first tubular element.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell comprises at least a first tubular element, at least a second tubular element and a spring element, preferably a compression spring, where the spring element is positioned so that it can move at least one second tubular element in the longitudinal direction relative to the first tubular element.

It should be understood that such a spring element, mainly within the shell, in particular in the inner space of the shell, preferably at least within the tubular element, is located in such a way that such a spring element applies a compressive force of the spring to the shell, in particular at least at least one first and / or at least one additional tubular element, which is sufficient for the movement of the second tubular element in the longitudinal direction relative to the first tubular element. The sealing layer and / or the trigger mechanism may prevent this spring from expanding or opening the shell. After dissolution and / or destruction of the upper part of the shell and / or the trigger mechanism, displacement of the tubular elements under the action of a spring may occur. Such a displacement of the tubular elements may lead to the opening of the membrane and / or release of the plate preparation. In particular, the drug can be enclosed in a smaller tube and subsequently pushed out of the shell, after which one or more additional drug tubes can be released. Alternatively, further appropriate steps can be carried out after moving the tube that releases the drug. In particular, the bias may serve as a release preparation. In this context, it should also be understood that a particular configuration may be selected depending on the desired final size of the dosage form and / or preparation.

Moreover, the shell and / or the first and / or additional tubular element may contain a mechanical stop that limits the displacement of the smaller second tubular element in the longitudinal direction relative to the first tubular element.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the shell comprises at least one connecting or lever element, which is preferably located at the free end of the shell.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the first connecting or lever element is located at the free end of the sheath.

In particular, the first connecting or lever element may be located on the free end of the shell, preferably on the free end of the first and / or additional tubular element, which contains a freely rotating lever.

In a preferred embodiment, the pharmaceutical dosage form of the present invention, the shell contains at least one additional connecting or lever element.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the first connecting or lever element and / or additional connecting or lever element is formed in the form of a butt joint, hinge and / or lever or comprises a butt joint, hinge or lever.

Preferably, the first connecting or lever element and / or at least the additional connecting or lever element can be combined in such a way that they can move the butt joint or lever in different, preferably in opposite, directions. The joining angle of the first connecting or lever element and / or at least an additional connecting or lever element, in particular with respect to the shell or its part, in particular with respect to the tubular element, can be chosen in this way and / or made with such the possibility, in particular, with the possibility of rotation, that the expansion of the plate preparation can be achieved and / or carried out by movement of the butt joint or lever. In particular, due to the movement of the butt joint or lever, the diameter of the preparation can be increased.

It is also contemplated within the scope of the present invention that a connecting or lever element, in particular a lever, can be directly pivoted by a spring element or intermediate elements.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the first connecting or lever element and / or additional connecting or lever element is at least partially covered by a trigger mechanism.

For example, in an initial state of a dosage form, a connecting or link element or a combination of connecting or link elements, in particular levers, can form a membrane of the dosage form or at least a portion thereof. Unwanted penetration of liquid into the dosage form within the connecting or lever element or connecting or lever elements can be avoided by applying hermetic coatings, conforming in shape or applying protective coatings to the inner and / or outer wall of the connecting or lever elements. Such hermetic or protective coatings may be destroyed after opening the shell, in particular, after the expansion of the expansion system and / or after the movement of the butt joint or lever of the connecting or lever elements, or may be previously dissolved.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, at least one first connecting or lever element and / or at least one additional connecting or lever element are arranged so that the corresponding connecting or lever element, in particular, a lever located on one end, directly adjacent to the connecting or lever element, in particular, to the lever located on the other end. Preferably, at least one first connecting or lever element and / or at least one additional connecting or lever element is mounted on the first or additional tubular element for rotation or rotation. Preferably, the tubular element may comprise a slot in which at least a portion of at least one first connecting or lever element and / or at least one additional connecting or lever element can move in a sliding manner, preferably by means of a spring, in particular in the direction of the end tube.

Preferably, the connecting or lever elements of the first tube and the connecting or lever elements of the second tube are arranged alternately in the closed state of the dosage form, so that preferably in the closed state the connecting or lever elements of the first tube and the connecting or lever elements of the second tube form a coating or sheath.

In particular, in such an arrangement, when the connecting or lever elements of the first tube or the connecting or lever elements of the second tube are alternately in the closed state of the dosage form, the length of the lever between the connecting or lever elements of the first tube and the connecting or lever elements of the second tube may exceed folded forms. It should be understood that the maximum length of the lever can be limited to half the length of the dosage form in the case when the lever or connecting elements are located opposite each other, and that, in particular, the maximum achievable increase can be less.

Alternatively, the connecting or lever elements of the first tube and the connecting or lever elements of the second tube can also at least partially overlap each other or overlap each other in the closed state, in which the connecting or lever elements are arranged so that they do not interfere with each other after release according to the present invention.

The location of the first and / or second tubular element and the location of the connecting and lever element can be selected, in particular, in such a way that the lever and connecting elements form a spiral structure that can be attached to the tubular element, which faces the observer, when observing the dosed form behind, therefore, when observing the smallest area of the dosage form. With such an arrangement, it would be advantageous if the connecting or linking elements of the first tube and the connecting or linking elements of the second tube alternate, preferably in the closed state of the dosage form, so that preferably in the closed state in which the connecting or linking elements of the first tube and the connecting or the lever elements of the second tube form a shell and / or coating, a spiral structure at the first end of the dosage form, in particular at the end of the first tubular element, and piralnaya structure at the end of the second tubular member are balanced rotationally symmetrical manner. In this context, it should be understood that preferably the connecting or lever element and / or at least one additional connecting or lever element cause the development of the plate preparation, which is folded, within the dosage form in the initial state, as a result of which the development of the plate preparation is predominantly ensured at a predetermined site of exposure and contacting the plate preparation with the mucous membrane or intestinal wall.

The lever or lever element referred to in the present description preferably refers to a mechanical force transducer, which is preferably a solid body that is articulated at a pivot point. The hinge, as used in the present description, preferably relates to the movable connection of two planes, in particular, two parts of the shell, preferably the edge of the shell. In particular, the hinge, preferably the connecting hinge of one or more connecting or lever elements, is arranged in such a way that the two parts of the casing are movably connected, for example, in order to seal the interior of the casing with a movable structural element, in particular parts of the casing. For this purpose, the hinge is formed so that it can withstand the load of the moving part and the force from movement. A hinge, as described herein, can be constructed as having one degree of freedom.

In the framework of the present invention, the connecting element, in particular, the lever, can be adapted to ensure contact of the plate preparation with a predetermined point of action, in particular, with the mucous membrane or intestinal wall, can be strengthened by connecting the connecting or lever elements located opposite each other other, in particular, levers, preferably containing at least one additional flexible element.

It should be understood that the movement of the mechanical expansion system and / or the connecting or lever element, preferably made as part of the release mechanism, is preferably actuated by a trigger mechanism. Such a trigger mechanism may, for example, contain a soluble polymer that blocks the mechanical expansion system and / or the connecting (s) or lever (s) element (s), in particular levers, in its or their initial positions relative to each other . When targeted contact with the fluid at a predetermined site of exposure, in particular with the fluid of the gastrointestinal tract, the polymer can peel off, and the spring element, if present, can actuate and / or carry out the movement of the mechanical expansion system and / or connecting or lever element, in particular, a lever. Additionally or alternatively, the mechanical expansion system and / or the connecting (s) or lever (s) element (s), in particular the levers, can be prestressed in the initial state and / or can at least form a spring element in this way that the energy stored in the mechanical expansion system and / or in the connecting or lever element, in particular in the lever, can therefore be released by actuating the trigger mechanism, and the mechanical expansion system and / or connecting or a lever element, in particular a lever, moves properly. For example, after actuating the trigger mechanism, the plate preparation can be released by expelling the tubular elements, which are at least partially telescopic, for example, by means of a spring element, by stretching and / or unfolding the plate preparation, which enters the shell in folded, due to the expansion mechanism and / or connecting or lever elements.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the plate preparation is cachet.

In particular, the dosage form preparation of the present invention can be formed in the form of a so-called wafer cachet. Such a cachet may correspond in shape to the uneven contour of the surface of a predetermined site of exposure, in particular, the mucous membrane, for example, the intestinal wall, rectum or vagina, after absorption of the liquid. In addition, the lamellar preparation of the dosage form of the present invention can be gelled or swellable.

In a preferred embodiment, the dosage unit preparation of the present invention is already flexible and elastic until it is released from the membrane and can absorb fluid entering the membrane, for example, from the gastrointestinal tract.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the thickness of the plate preparation is from 0.01 mm to 2 mm, preferably from 0.03 mm to 1 mm, preferably from 0.05 mm to 0.1 mm.

In particular, platelet preparations of relatively small thickness have an advantage.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the surface area of the plate preparation is from 0.5 to 25 cm ² , preferably from 1 to 10 cm ² .

The plate preparation may take various forms. In particular, the plate preparation may have a round, triangular, rectangular or polygonal shape.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, a lamellar, in particular film, foil or wafer, preparation that contains an active pharmaceutical ingredient, contains an active pharmaceutical ingredient with an active substance content of from 0.5 to 40 mass. %, preferably from 1 to 30 mass. % and most preferably from 5 to 20 mass. %

In a preferred embodiment of the pharmaceutical dosage form of the present invention, a lamellar, in particular film, foil or wafer, preparation containing the active pharmaceutical ingredient has a single or multi-layer structure of one or more layers, where at least one (preferably first) layer contains the active pharmaceutical ingredient.

It should be understood that such a first layer containing the active pharmaceutical ingredient may be any layer of a multilayer preparation relative to its configuration and that, in particular, such a layer is not limited to the outer, inner, lower or upper layer.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the lamellar, in particular film, foil or wafer preparation, which contains the active pharmaceutical ingredient, is a multi-layer multi-layer structure in which at least an additional layer contains at least an additional active pharmaceutical ingredient.

The present invention also contemplates the active pharmaceutical ingredient contained in the first layer, which is similar to and different from the active pharmaceutical ingredient contained in the additional layer. In particular, the dosage unit preparation of the present invention may be embodied as a so-called combination of plates and may contain a combination of active pharmaceutical ingredients in one layer or in several layers separately or together.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the lamellar, in particular film, foil or wafer, preparation containing the active pharmaceutical ingredient contains at least a first layer containing the active pharmaceutical ingredient and / or an additional layer containing the active substance, wherein the first layer containing the active substance and / or the additional layer containing the active substance is a polymer, preferably film binder polymer.

Such a polymer layer, preferably a film-forming polymer, advantageously serves as a reservoir for the active substance, wherein such a layer can release the active pharmaceutical ingredient when exposed to a liquid.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the lamellar, in particular film, foil or wafer, preparation containing the active pharmaceutical ingredient contains at least one first layer containing the active ingredient and / or an additional layer containing the active ingredient, wherein at least one first layer containing the active ingredient and / or an additional layer containing the active ingredient is a polymer, wherein th polymer in the at least one first layer containing the active ingredient and / or an additional layer containing an active ingredient which comprises a polymer of at least 10 to 90 wt. %, preferably from 20 to 70 mass. % and most preferably from 30 to 60 mass. %

In a preferred embodiment of the pharmaceutical dosage form of the present invention, a lamellar, in particular film, foil or wafer, preparation containing the active pharmaceutical ingredient, contains at least a first layer containing the active ingredient, and / or an additional layer containing the active ingredient, where at least one first layer containing the active ingredient and / or an additional layer containing the active ingredient is an adhesive layer.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, at least one first layer containing the active ingredient and / or an additional layer containing the active ingredient comprises a polymer, preferably a film-forming polymer, which is water soluble and / or water degradable and / or water degradable .

The polymer for the first layer containing the active substance and / or for the additional layer containing the active substance, in particular, may be selected from the group consisting of polyvinyl alcohols, polyvinyl pyrrolidone, polyvinyl acetate, polyethylene glycol, polyethylene oxide polymers, polyurethanes, polyacrylic acids, polyacrylates, polymethacrylates, poly (methyl vinyl ester anhydrides and maleic acid), starch, starch derivatives, natural gums, alginates, pectins and gelatin, pullulan, gelling proteins, hit bonded, agar, agarose, carrageenan, xanthan, tragacanth, dextran, and cellulose ethers such as ethylcellulose, gidroetiltsellyuloza, propylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, cellulose acetate, povidone and copovidone.

For the manufacture of a lamellar preparation for a dosage form of the present invention with desirable properties such as adhesive properties, release properties, or disintegration properties, polymers can be used either individually or in combination with each other. In particular, the lamellar preparation of the present invention may consist of a single polymer layer. In addition, the lamellar preparation for the dosage form of the present invention may have a structure with two or more layers when at least one of the layers contains an active pharmaceutical ingredient. If several layers contain an active pharmaceutical ingredient or active pharmaceutical ingredients, they may differ from each other in terms of their content of active ingredient and combination of active ingredients, as well as in their polymer composition and, therefore, in their adhesive and / or disintegration properties.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, a lamellar, in particular film, foil or wafer, preparation containing an active pharmaceutical ingredient, contains at least one first active ingredient-free layer that does not contain an active pharmaceutical ingredient.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, a lamellar, in particular film, foil or wafer, preparation containing the active pharmaceutical ingredient, contains at least an additional active ingredient-free layer that does not contain an active pharmaceutical ingredient.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the first layer containing no active ingredient and / or at least one additional layer containing no active ingredient is a water-insoluble layer, which preferably contains water-insoluble substances selected from the group consisting of ethyl cellulose and / or combinations of ethyl cellulose with other water insoluble substances, hydrophobic plasticizers, in particular triethyl citrate, and / or crystals, and / or flavors and / or flavors.

In particular, the use of ethyl cellulose may be appropriate due to its properties such as processability, biocompatibility and water insolubility.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the first layer containing no active ingredient and / or at least one additional layer containing no active ingredient is an adhesive layer that preferably contains hydroxypropyl methylcellulose.

The adhesive layer may vary in its desired thickness. Additionally or alternatively, the adhesive layer may be a mucoadhesive polymer selected from the group consisting of cellulose derivatives, starch and starch derivatives, polyvinyl alcohol, polyethylene oxide, polyethylene, polypropylene, polyacrylic acid and polyacrylate derivatives, polyvinyl pyrrolidone, polyvinyl pyrrolidone, sodium povidone alginine, copelidin, gelatin , xanthan gum, carrageenan, pectins, dextrans, lectins, chitosan, pullulan, as well as mixtures of these substances.

The adhesive layer may also vary in its desired thickness. Additionally or alternatively, the adhesive layer may contain a solvent which is selected from the group consisting of water, ethanol, methanol, acetone, organic solvents, as well as a mixture of these substances.

Moreover, the adhesive layer may additionally contain auxiliary substances, such as colorants, flavors, flavorings, preservatives, antioxidants, absorption enhancers, solvents, decomposition accelerators, blowing agents, lubricants, and also mixtures of these substances.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the plate preparation has a multilayer structure, preferably with two or three layers, and contains at least one layer containing the active substance and at least one layer containing no active ingredient.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the lamellar preparation has a multilayer structure, preferably with three layers, where the first layer containing the active ingredient is located between the first layer containing no active ingredient and / or an additional layer containing no active ingredient, where the first layer containing no active ingredient is preferably a water-insoluble layer that preferably contains ethyl cellulose, and at least one additional layer not containing active ingredient is an adhesive layer which preferably comprises a hydroxypropyl methylcellulose.

The medicament of the present invention, in particular the plate preparation, may further comprise one or more excipients. In particular, the following substances can act as auxiliary substances: lubricants, glidants, binders, additional active substances, disintegrants, antioxidants, chelating agents, coating agents, flow improvers, preservatives, fillers, surfactants, plasticizers and pigments . In addition, excipients can be selected from the following group: blowing agents, absorption enhancers, solvents, emulsifiers containing polyethoxylated sorbitol fatty acid esters, ethoxylated fatty alcohols, as well as lecithin; plasticizers containing polyethylene glycol, glycerin and other polyhydric alcohols, higher alcohols such as dodecanol, undecanol or octanol, sorbitol, mannitol and other sugar alcohols, dexpanthenol and triglycerides; fillers containing highly dispersed silicon dioxide, titanium dioxide, zinc oxide, chalk or starch; dyes; sweeteners and flavorings; wetting agents; preservatives; pH regulators and antioxidants; decay accelerators; absorption enhancers that promote the absorption of estradiol into the mucous membrane, for example, fatty acids and fatty acid esters, polyhydric alcohols such as propanediol, tocopherols or essential oils such as menthol.

The content of these auxiliary substances can be up to 60 mass. % relative to the total weight of the plate preparation. Preferably, the content of auxiliary substances is from 5 to 40 mass. % By adding one or more of the above excipients, one of skill in the art can significantly affect the chemical and physical properties of a drug film-like preparation containing the active ingredient, such as, for example, desired flexibility, adhesive ability, swelling ability, degradability, as well as diffusion properties, and adjust these properties.

In accordance with a preferred embodiment of the pharmaceutical dosage form, in particular the lamellar preparation of the present invention, it is contemplated to use a sustained release of the active ingredient. The active pharmaceutical ingredient is preferably released within 4 hours, preferably within 6 hours, and most preferably within 8 hours. In order to provide a sustained release of the active ingredient in the case of bilayer or trilayer preparations, at least one of the layers containing the active ingredient, in particular the polymer layer, has a slow release of the active ingredient.

For sustained release of the active ingredient, the film-like pharmaceutical preparations are preferably in the form of a slowly soluble or slowly disintegrating film, which completely disintegrates or dissolves after only a few hours. Preferably, complete decomposition or complete dissolution occurs only after 4 hours, preferably only after 6 hours, and most preferably only after 8 hours or even only after 24 hours, or more.

According to an alternative preferred embodiment of the pharmaceutical dosage form of the present invention, in particular, the lamellar preparation is a quick-release dosage form that releases the active pharmaceutical ingredient within 1 hour, preferably within 30 minutes and most preferably within 5 minutes. For the rapid release of the active ingredient, the preparation in the form of a film may preferably be in the form of a rapidly dissolving or rapidly disintegrating film. The lamellar preparation can be made with the possibility of almost complete disintegration, transition to a gel state or dissolution, preferably within a few minutes after release. Preferably, the lamellar preparation completely disintegrates, passes into a gel state or completely dissolves within 1 hour, preferably within 15 minutes and most preferably within 5 minutes.

In accordance with a preferred embodiment, the film-like drugs of the present invention are adhesive, in particular mucoadhesive. An embodiment which only contains an adhesive, in particular mucoadhesive, preparation is particularly preferred. Due to this, when applied, adhesion of the dosage form to a predetermined site of exposure, in particular to the mucous membrane, is achieved, and absorption of the active pharmaceutical ingredient or active pharmaceutical ingredients, in particular through the mucous membrane, can occur directly at a predetermined site of exposure.

Moreover, on the opposite side of the adhesive, in particular mucoadhesive, surface, the lamellar preparation may contain a layer impervious to the active pharmaceutical ingredient, so that when applied at a predetermined site of exposure, the targeted release of the active ingredient can be achieved.

A pharmaceutical dosage form, in particular a plate preparation, can be prepared by a person skilled in the art by known methods, for example, by coating an inert support with a liquid composition containing the polymer (s), active ingredient (s) and optionally auxiliary (s) substance (s) and solvent (s), for example, using a knife device, spraying or extrusion devices. The thin film obtained in this way is dried. In the case of a multilayer plate preparation in the same way, one or more coatings can be applied to the existing film layer or these layers can be made separately and subsequently layered.

A pharmaceutical dosage form, in particular a shell and / or plate preparation, may further comprise at least one adjuvant masking the taste of the drug. This advantageously allows you to fix the bitter or otherwise unpleasant taste of the active pharmaceutical ingredient, but may also be appropriate to accelerate the onset of action of the active pharmaceutical ingredient. Excipients that mask the taste of the drug are known to those skilled in the art. Such adjuvants masking the taste of the drug, in particular, contain a sugar alcohol selected from mannitol, sorbitol, xylitol, malitol, lactitol, erythritol, threitol and isomalt, as well as sodium bicarbonate.

The active pharmaceutical ingredient that is contained in the plate preparation of the pharmaceutical dosage form of the present invention may, in particular, be selected from the group consisting of proteins and peptides, in particular insulin, buserelin, desmopressin, calcitonin and estrogen, as well as substances made in a biotechnological manner, such as antibodies, for example, rituximab. It should be understood that proteins and peptides, in particular, insulin, buserelin, desmopressin, calcitonin and estrogen, may under certain conditions exhibit low - in particular, low when taken orally - bioavailability, as a result of which they are suitable candidates for use with dosed forms of the present invention.

Substances from the following groups are particularly suitable as active pharmaceutical ingredients: drugs that act on the skeleton and muscles, drugs that act on the nervous system, hormones and drugs that act on the hormonal system, drugs that have a gynecological effect, drugs that act on the cardiovascular system, drugs on the respiratory system, drugs on the gastrointestinal tract echny tract, diuretics, drugs that act on the sense organs, transdermal preparations, vitamins and minerals, peptide drugs and proteins, analgesics, anti-infective and anti-parasitic drugs.

In particular, the plate preparation may have at least a first region and at least a second region, where at least one first region contains an active pharmaceutical ingredient. Preferably, at least one second region contains an additional active pharmaceutical ingredient that is different from the active pharmaceutical ingredient of at least one first region of the plate preparation. It is also preferred that at least one second portion does not contain an active pharmaceutical ingredient of at least one first portion of the plate preparation. In an alternative and preferred embodiment, the at least one second region contains the active pharmaceutical ingredient of at least one first region of the plate preparation with a concentration in area, volume or mass different from the concentration of the active pharmaceutical ingredient of the first region.

It should be understood that in this context, active pharmaceutical ingredients may also refer to mixtures of active pharmaceutical ingredients and / or excipients. Thus, at least one second portion of the plate preparation may comprise a mixture that is different from a mixture of at least one first portion. In particular, mixtures of at least one first region and at least one second region may differ in the composition of the active pharmaceutical ingredients and / or excipients, as well as in the number of corresponding active pharmaceutical ingredients and / or excipients.

In particular, this allows the release of various active pharmaceutical ingredients in different parts of the body, in particular on different mucous membranes or different parts of the mucous membranes, such as buccal, gastroenteric, intestinal, rectal or vaginal mucous membranes, with a single pharmaceutical dosage form. Preferably, one active pharmaceutical ingredient or one mixture of active pharmaceutical ingredients can be applied to the first portion of the vaginal mucosa, which is closer to the cervix than the second portion of the vaginal mucosa, and another active pharmaceutical ingredient or other mixture can be applied to the aforementioned second portion. Moreover, active pharmaceutical ingredients may not be released in the first or second portion of the vaginal mucosa. In an alternative and preferred embodiment, the first portion of the plate preparation may come into contact with the mucous membrane of the esophagus, and the second portion of the plate preparation may come into contact with the buccal mucosa. Thus, one active pharmaceutical ingredient can be used on the mucous membrane of the esophagus, while another active pharmaceutical ingredient can be applied on the buccal mucosa, no other active pharmaceutical ingredient is applied, or an excipient can be released on the buccal mucosa. In particular, a flavoring and / or local anesthetic may be released, in particular to increase or decrease the production of saliva and / or to make the use of the pharmaceutical dosage form more enjoyable and / or to suppress the emetic urge.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, wherein the plate preparation contains at least a first region and at least a second region, the second region may comprise an additional active pharmaceutical ingredient that counteracts the active pharmaceutical ingredient of the first region. This may be appropriate to suppress the systemic action of the active pharmaceutical ingredient of the first site. In particular, the fluid that runs along the mucous membrane can pass first in the first section and then in the second section, and therefore, can, firstly, absorb the active pharmaceutical ingredient of the first section, which is subsequently counteracted, preferably neutralizes the active pharmaceutical ingredient of the second plot. In particular, such an active pharmaceutical ingredient that counteracts another pharmaceutical ingredient may be selected from the following list: enzymes that break down the active pharmaceutical ingredients, such as esterases; ions that complex with other active pharmaceutical ingredients, such as calcium, iron or magnesium; sympathomimetic and sympatholytic drugs; parasympathomimetic and parasympatolytic drugs; antibodies that bind drugs; drugs for treating side effects of one active pharmaceutical ingredient without counteracting another active pharmaceutical ingredient. In an alternative and preferred embodiment, the plate preparation may likewise comprise a first layer with an active pharmaceutical ingredient and a second layer with an additional active pharmaceutical ingredient that counteracts the active pharmaceutical ingredient of the first layer. In this case, the above advantages can be achieved when the action of the active pharmaceutical ingredient of the first layer is directed to or from the mucous membrane.

In a preferred embodiment of the present invention, the pharmaceutical dosage form is adapted for use on the upper gastrointestinal tract, such as the pharynx, esophagus, cardia and / or stomach, and especially on the respective mucous membranes and / or preferably on the buccal and / or esophagus mucous membrane.

In a preferred embodiment, the pharmaceutical dosage form of the present invention is adapted for use on the nasopharyngeal mucosa.

In a preferred embodiment, the pharmaceutical dosage form of the present invention or a part thereof, in particular a dosage form for use on a buccal or esophageal mucosa, is in a form that can be swallowed.

In particular, a capsule shell can be swallowed. Preferably, the circumference of the capsule is less than 6 cm, preferably less than 3 cm and preferably less than 2 cm, and also more than 0.2 cm, preferably more than 0.5 cm and preferably more than 1 cm. Preferably, the longitudinal axis of the capsule is shorter than 5 cm, preferably shorter than 3 cm and preferably shorter than 2 cm, and also preferably longer than 1.5 cm. In particular, the shell may be shaped in accordance with a standard capsule shape, such as 00, 0, 1 or 3, the length of which is from 16.1 mm up to 23.5 mm and a circumference of 17.9 mm to 26.7 mm. Similarly, the pharmaceutical dosage form or part of the pharmaceutical dosage form for ingestion may be curly. In addition, to ensure ingestion, a smooth or sliding surface of the shell, dosage form or part of the dosage form may be appropriate.

This advantageously allows oral administration of the pharmaceutical dosage form of the present invention. In particular, only the dosage form or part of the dosage form, preferably the shell, can be swallowed. In this context, it should be understood that some parts of the dosage form can be made with the possibility of swallowing, while other parts of the dosage form may not be suitable for swallowing.

In a preferred embodiment, the pharmaceutical dosage form of the present invention, in particular the dosage form for use on the buccal or esophageal mucosa, on the nasopharyngeal mucosa, on the gastrointestinal mucosa, on the rectal or vaginal mucosa, the lamellar preparation contains at least one active a pharmaceutical ingredient selected from the group of the following substances: substances for diagnosis, such as dyes or contrast agents, more anti-inflammatory drugs, preferably non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or flurbiprofen; local painkillers such as benzocaine, butamben, dibucaine, lidocaine, oxybuprocaine or novocaine; antibiotics such as penicillin, amoxicillin or vancomycin; antiseptics such as 2,4-dichlorobenzyl alcohol, amyl methacresol or cetyl pyridinium chloride; steroids such as corticosteroids, glucocorticoids, fluticasone, budesonide, clocortolone, perdesonide, hydrocortisone, clobetasone butyrate, hydromethysone acetonate, hydrocortisone buteprate, hydrocortisone 17-butyrate-acetazone-triazone-triazone-diacetamide 17-valerate, deoxymethasone, diflucortolone-21-valerate, fluocinolone acetonide, fluocinonide, fluticasone-17-propionate, methylprednisolone aceponate, mometasone furoate, predicarbate or clobetasol-17-propionate; antiparasitics, which are also called parasiticides, such as mebendazole, albendazole, thiabendazole, diethylcarbamazine, diaminodiphenylsulfone, benznidazole, ivermectin, pyrantel, praziquantel; antifungal agents such as nystatin, imidazole, triazole, clotrimazole, ketoconazole or undecylenic acid; crystalline violet base, amphotericin B, botulinum toxin, sucralfate, nitric oxide or nitric oxide forming substances such as isosorbide dinitrate or nitroglycerin, furanocoumarins, benzoic acid, citric acid, lactic acid, pH buffers, antacids, calcium carbonate, magnesium carbonate or aluminum carbonate. Additionally or alternatively, the lamellar preparation may separately contain an inflammation regulator, such as montelukast, interleukin receptors or interleukin antibodies. Additionally or alternatively, the lamellar preparation may separately contain beclomethasone dipropionate, budesonide or cyclesonide, which is especially useful for treating asthma. Additionally or alternatively, the plate preparation may separately contain mesalazine, sulfasalazine or olsalazine, which is especially useful for treating inflammatory bowel disease.

In particular, a plate preparation containing a specific active pharmaceutical ingredient advantageously provides a treatment, preferably topical, of the corresponding disease or infection. Thus, the specific active pharmaceutical ingredient can be applied at the appropriate place of application, in particular on the mucous membrane, and the local concentration and / or therapeutic effect can be increased, and / or side effects, in particular undesirable reactions, can be reduced by compared to systemic use. In this context, it should be understood that, in addition to local action, a systemic effect is also possible, preferably due to the absorption of the active pharmaceutical ingredient through the mucous membrane into the body. Moreover, in a preferred embodiment, the plate preparation may contain various active pharmaceutical ingredients, wherein at least one active pharmaceutical ingredient is selected so that it remains at least substantially localized in the mucosa and / or within the mucosa, while while at least another active pharmaceutical ingredient is selected so that it enters the body through the mucous membrane, as a result of which, in particular, exerts a systemic effect.

A preferred embodiment of the pharmaceutical dosage form of the present invention provides for oral administration. As a consequence, the dosage form or part of the dosage form, in particular the shell, has a swallowable form. Preferably, the dosage form is formed as described above. Moreover, this preferred embodiment may contain, in the form of an active pharmaceutical ingredient or active pharmaceutical ingredients, a drug that is traditionally not suitable for oral administration, in particular due to low bioavailability or highly variable intraindividual plasma concentration. Among these drugs are: proteins and peptides, such as insulin, buserelin, calcitonin or desmopressin, which is also called osmopressin; hormones such as estrogen; as well as biotechnological drugs, such as antibodies, in particular rituximab.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, in particular a dosage form for use on the mucous membrane, in particular the buccal, esophageal, rectal or vaginal mucosa, the lamellar preparation provides a relatively large surface area after release by the release mechanism. In particular, the lamellar preparation is configured to come into contact with a relatively large surface area, preferably the mucous membrane, preferably at a predetermined release site or site of exposure, after its release by the release mechanism. Therefore, and preferably, the plate preparation can cover a relatively large surface area of the mucous membrane, in particular, relatively large compared to the volume of the plate preparation and / or the amount of active pharmaceutical ingredients. Some of the individual benefits are already described above. In particular, increased absorption of the active pharmaceutical ingredient contained in the plate preparation can be achieved. Moreover, in a preferred embodiment, in particular with a multilayer plate preparation, the release of the active pharmaceutical ingredient can be directed into the mucous membrane. Thus, the local concentration of the active pharmaceutical ingredient and / or bioavailability and / or absorption rate and / or local action can be increased. Moreover, the concentration of the active pharmaceutical ingredient in a liquid that is present near the mucous membrane can be reduced by targeted release, and thus side effects can be reduced, and / or bioavailability can be increased, and / or local action can be enhanced.

The term "relatively large", as used in the present description, indicates that one element is larger than another element, and / or that one element is larger than such an element or corresponding parameter, in the traditional embodiment of this element, where preferably scale, spatial extent, length, area, volume, surface area, cross-sectional area, envelope cross-sectional surface, contact surface area, covering surface area, diameter, circumference, circumference The sectors, size, quantity, content, functional activity and / or average size or area of action are preferably at least more than 125%, preferably at least 200%, preferably at least 500%, preferably at least 1000% and preferably at least 5000%. In particular, the relatively large surface area of the plate preparation of the present invention is larger than the surface area of a conventional dosage form or a preparation included therein. In particular, the surface area of the plate preparation of the present invention can be relatively large compared to the volume of the plate preparation. In particular, the area, preferably the surface area, can be compared with the corresponding volume. Preferably, the area is relatively larger than the volume, if the square root of the surface area is larger than the cubic root of the volume, preferably at least 125%, preferably at least 200%, preferably at least 500%, preferably at least at least 1000% and preferably at least 5000%. Additionally or alternatively, the relatively large surface area of the plate preparation mainly refers to the surface area of the plate preparation, which is larger than the surface area of a traditional dosage form or such preparation with the same amount of active pharmaceutical ingredient, preferably as many times as described above. It should be understood that the surface area of the plate preparation is at least preferably a continuous surface area, while, in particular, the powder may also have a large surface area, which, however, is not a substantially closed surface area, but rather a huge the number of small surface areas of the individual powder particles. In particular, subject to appropriate changes, this is also true for a drug or active pharmaceutical ingredient that dissolves in a liquid. In particular, contact with a relatively large surface area, in particular with the mucous membrane, means that the contact surface area and / or the surface area, in particular coated with a flat preparation, is greater than the surface area that may come into contact and / or may be It is covered with a traditional dosage form or a drug included in it. In particular, if the traditional dosage form can dissolve in a liquid, then this liquid may have a large contact surface area with a corresponding mucous membrane, however, the surface area cannot be predominantly continuous surface area, as described above, and / or the concentration of the drug or active pharmaceutical ingredient in the above liquid may be lower than the concentration in the plate preparation and / or in the mucous membrane coated with the plate preparation, and / and and a fluid filling the gap between the plate and the coated preparation corresponding to the mucosal surface.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, in particular a dosage form for use on the buccal, esophageal, nasopharyngeal, intestinal, rectal or vaginal mucosa, the release mechanism is configured to release the lamellar preparation while moving along the mucous membrane. It should be understood that the plate preparation can only be partially released during movement along the mucous membrane. It should also be understood that the pharmaceutical dosage form or only part of the pharmaceutical dosage form, in particular, the release mechanism and / or lamellar preparation or its part, can move along the mucous membrane. In addition, release may occur only during part of the movement. In particular, the movement can occur along a path, preferably along a predetermined path, and preferably the release of the plate preparation or part thereof occurs along a given path or part of the path. In addition, movement can be active or passive.

The term "active movement" as used in the present description, preferably refers to the movement that actively carries out the dosage form or its part, preferably due to the actuator or device for moving the dosage form. Thus, in particular, the pharmaceutical dosage form or part thereof generates an effort to effect movement.

The term “passive movement” as used herein preferably refers to movement caused by external forces and / or movements. In particular, with passive movement, the dosage form or part of it moves due to external movements and forces. Preferably, such external movement and / or force may be gravity, movement of the mucous membrane, movement of fluids present at a predetermined launch site, place of application or place of exposure, movement of muscles, in particular muscles that are close to the organ with the corresponding mucosa shell or belonging to this body, or the efforts developed by such movements. Preferably, this organ may be an esophagus in which the musculature of the esophagus moves, in particular when swallowing, and thereby generates force, preferably with the help of the mucous membrane of the esophagus and / or with a liquid, in particular a liquid such as drinks, water or saliva, where the force acts on the dosage form or part thereof when it is within or near the esophagus, preferably in the mouth. Also preferably and / or alternatively, the organ may be a nose, throat or nasopharynx, where air inhaled through the nose or mouth moves the pharmaceutical dosage form or part thereof.

In particular, this advantageously ensures the release of the plate preparation along an extended, in particular elongated or elongated, section of the mucous membrane. Preferably, the plate preparation may be released along the path of the pharmaceutical dosage form or part thereof. This trajectory is preferably predetermined by the structure and / or movement of the mucous membrane or organ and / or fluid contained in the lumen of the aforementioned mucous membrane or the aforementioned organ. Thus, in a preferred embodiment, the active pharmaceutical ingredient can be released along an elongated, in particular elongated or elongated, section and / or along the path of the mucous membrane. Therefore, and preferably, to a spatially extended area of the mucous membrane or organ can be applied, in particular, local treatment. Moreover, in an alternative or further improved preferred embodiment, the lamellar preparation can release the active pharmaceutical ingredient locally at the aforementioned site and / or after a prolonged time. Another advantage may arise from the fact that upon release of the plate preparation during movement, the plate preparation can be aligned in the direction of movement, in particular along the path of movement. In particular, for a dosage form in which the plate preparation contains the first and second sections, such sections may be located in different sections of the mucous membrane and / or along different motion paths. In addition, in particular, due to the release of the plate preparation during passive movement, the risk of damage can be reduced.

In particular, the active pharmaceutical ingredient can be used to treat the esophagus, for which it is topically applied to the mucous membrane of the esophagus. So, in particular, the active pharmaceutical ingredient can be applied to the expanded area of the mucous membrane of the esophagus. Moreover, the active pharmaceutical ingredient may have a local effect on the mucous membrane of the esophagus. Thus, side effects due to the systemic effect of the active pharmaceutical ingredients can be reduced, and / or the local effect on the mucous membrane of the esophagus, in particular in connection with a locally increased concentration of the active pharmaceutical ingredient, can be enhanced. Moreover, if the lamellar preparation releases the active pharmaceutical ingredient locally and / or prolonged, the effectiveness of the treatment can be increased, and in particular, the local effect of the active pharmaceutical ingredient can be enhanced. To this we can add that, in particular, due to the spatially expanded scope, the need for systemic administration of the drug can be reduced. Even more specifically, esophagitis, in particular eosinophilic esophagitis, can be treated with such a pharmaceutical dosage form. In this case, the drug, in particular the active pharmaceutical ingredient, can be directed to the mucous membrane of the esophagus and / or can be preferably selected from the group consisting of: steroids such as corticosteroids, glucocorticosteroids, fluticasone, budesonide, clocortolone, perdesonide, hydrocortisone , clobetasone butyrate, flumethasone, flupredniden, hydrocortisone acetonate, hydrocortisone buteprate, hydrocortisone-17-butyrate, triamcinolone acetonide, amcinoid, betamethasone-17,21-dipropionate, betamethasone-17-valerate, de oksimetazon, diflucortolone 21-valerate, fluocinolone acetonide, fluocinonide, beclomethasone-17-propionate, methylprednisolone aceponate, mometasone furoate, prednicarbate or clobetasol-17-propionate; nitric oxide or substances that form nitric oxide, such as isosorbide dinitrate or nitroglycerin, beclomethasone dipropionate, cyclesonide, pH buffers, antacids, calcium carbonate, magnesium carbonate or aluminum carbonate. Additionally or alternatively, the plate preparation alone may contain an inflammatory regulator, such as montelukast, interleukin receptors or interleukin antibodies.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, in particular a dosage form for use on the buccal and / or esophagus mucosa and / or nasopharyngeal mucosa, the release mechanism comprises a sectional element, where the sectional element increases from compact to expanded. In particular, after the release mechanism has been actuated, the sectional element can be enlarged to a deployed shape using another part of the release mechanism or due to external movement and / or force, preferably due to the movement of fluids at a predetermined starting point, the movement of the mucous membrane or gravity . Preferably, the sectional element comprises a plate preparation. The sectional element may comprise a plate preparation in compact form and / or in expanded form. Alternatively or preferably, the plate preparation may be configured to form a sectional element. Thus, the sectional element contains an active pharmaceutical ingredient. It should be understood that the sectional element can only partially contain a plate preparation or the plate preparation can only partially form a sectional element. In addition, only a part of the sectional element can be converted from a compact form to an expanded form, while at least one or another part of the sectional element remains in a compact form or in expanded form.

The term "compact form", as used herein, preferably refers to a folded shape, a rolled shape, a twisted shape, a rolled shape, or a compressed shape. In particular, the plate preparation has a smaller spatial extent and / or has an effect on a smaller surface area than in a form that is not compact, in particular in an expanded form. Preferably, the plate preparation in a compact form is folded, compressed, folded, twisted, rolled up, pressed, crumpled, or reduced to a smaller format in another way. In particular, in a compact form, the plate preparation may have a predetermined size or spatial extent.

The term “expanded shape” as used herein preferably refers to an expanded shape, an expanded shape, an expanded shape, an extended shape, an elongated shape or an elongated shape. In particular, in expanded form, the lamellar preparation has a greater spatial extent and affects a larger surface area than in non-expanded form, in particular in a compact form. Preferably, the lamellar preparation in expanded form is deployed, distributed, opened, untwisted, unwound, opened, extended, extended, expanded, or reduced to a larger format in another way. In particular, the plate preparation may have a predetermined size or spatial extent when it has an expanded shape. Alternatively, the size or spatial extent of the plate preparation may depend on current conditions, as well as on the site of exposure or place of use, and thus may not be predetermined.

The sectional element has the advantage of allowing the active pharmaceutical ingredient to be released, in particular into the mucous membrane that surrounds a fairly small lumen or cavity, such as the esophagus or nasal cavity. Moreover, the compact form of the sectional element advantageously allows the creation of a relatively small pharmaceutical dosage form, in particular for oral administration, which helps to swallow the dosage form. In addition, the sectional element can be enlarged, in particular, expanded, unwound, unwound, stretched or stretched, to the expanded form, thereby ensuring the release of the active pharmaceutical ingredient to an elongated region of the mucous membrane, in particular, to the mucous membrane of the cheek and / or esophagus and / or nasopharynx. In particular, it is advisable that the surface area exposed and / or the length of the sectional element or plate preparation exposed to the environment, in particular the mucous membrane, increase when the sectional element increases, in particular, stretches or stretches, from a compact form to the expanded form. Due to this advantage, the active pharmaceutical ingredient is protected in a compact form and / or the release of the active pharmaceutical ingredient is enhanced due to the rather large and / or long contact surface area in expanded form. An advantage of such a preferred embodiment is the use of a sectional element for securing and / or transporting the plate preparation, and thus, in particular, in providing the choice of various substances and compositions for the plate preparation. Another advantage of the alternative and preferred embodiment comes from the fact that the lamellar preparation forms a sectional element, and thus, in particular, provides the opportunity to reduce the number of components of the dosage form and it is preferable to simplify the manufacture of the release mechanism and / or lamellar preparation.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the lamellar preparation, in particular in expanded form, is formed in the form of a thread, cord, strip or tube. Preferably or alternatively, the plate preparation is bendable.

In an additional improved or alternative embodiment of the pharmaceutical dosage form of the present invention, the lamellar preparation is configured to form, in particular, in expanded form, a thread, cord, strip or tube. Preferably, the lamellar preparation is bendable so that it can transition from a compact form, in particular with a folded, compressed, folded, twisted or rolled lamellar preparation, which may preferably be in the form of a thread, cord, strip or tube, into an expanded form.

In particular, this has the advantage of allowing the dosage form to be applied and the lamellar preparation to be released onto the mucous membrane, which has a rather small clearance (cavity), in particular with a smaller diameter, and / or to treat the mucous membrane or organ with this mucous membrane, which exhibit the opposite effect in the case of covering large areas of the mucosa or clogging its lumen or part of the plate preparation. In particular, such a side effect may be a vomiting reflex, sneezing reflex or obstruction to a fluid such as a liquid solution, water, intestinal juices or air. Another advantage is the possibility of simplified manufacturing. Additionally and preferably, the spatial extent of the expanded form, in particular, the length of the plate preparation in its expanded form, in particular along its longitudinal axis or axis of extension, can be significantly greater than the spatial length of the compact form, in particular, the maximum diameter of the plate preparation in compact form. The term "significantly larger", as used herein, preferably refers to a ratio that is greater than or equal to 3: 1, preferably 6: 1, preferably 10: 1, preferably 20: 1, preferably 30: 1, in particular, refers to an aspect ratio, area ratio or volume ratio.

It should be understood that it may also be advisable to limit the maximum spatial expansion and thereby limit the ratio to preferably 200: 1, preferably 100: 1, preferably 60: 1, and preferably 40: 1. Thus, in particular, in the case where the volume of the plate preparation remains constant, a minimum cross-sectional diameter can be provided that is at least substantially orthogonal to the longitudinal axis of the plate preparation in its expanded form. On the other hand, in the case of a plate preparation, which, at least in its expanded form, is made in the form of a tube with a relatively large diameter, preferably with a diameter that corresponds to the diameter of the corresponding lumen surrounded by the corresponding mucous membrane, the mucous membrane can be covered with a large the amount of the preparation compared to a lamellar preparation of a smaller diameter, for example, a sectional lamellar preparation.

In a preferred embodiment of the present invention, the pharmaceutical dosage form, at least in expanded form, is longer than 5 cm, preferably longer than 10 cm, preferably longer than 30 cm and preferably longer than 40 cm, and also preferably shorter than 95 cm, preferably shorter than 70 cm and preferably shorter than 50 cm. In this context, it should be understood that the dosage form and, in particular, the lamellar preparation, at least one end of which must be kept during ingestion, requires that the length of the plate the lamellar preparation was correspondingly longer than the above dimensions, preferably at least 5 cm, preferably at least 10 cm and preferably at least 20 cm. Thus, the lamellar preparation may preferably have a length of at least substantially 60 cm .

In this context and / or in the present description, the term "length" or terms related to length, such as "longer", "shorter" preferably refer to the length measured along the longitudinal axis and / or the axis of expansion, and / or the axis of increase of the corresponding an object, in particular, a plate preparation. Specifically, the length of the plate preparation in its expanded form, preferably in an elongated form, can be measured using a measuring tape. More specifically, the plate preparation may have a first and second end, and a measuring tape for measuring the length of the plate preparation may be directed along the plate preparation from the above first end to the second end. In particular, when the corresponding object, for example, a plate preparation, is located at least essentially in a straight line, the length of the corresponding object is the length along this line. Specifically, if the length is the longest spatial expansion, the direction of the above straight line corresponds to the longitudinal axis.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the area and / or surface area of the plate preparation is from 0.5 to 25 cm ² , preferably from 2 to 25 cm ² , preferably from 5 to 25 cm ² , preferably from 5 to 15 cm preferably more than 0.5 cm and preferably less than 40 cm ² . Preferably, the ratio of the length and width of the plate preparation is from 40: 1 to 400: 1, preferably from 60. T to 300: 1, or preferably from 80: 1 to 200: 1. The above width may be the average width of the plate preparation, measured, for example, perpendicular to the length of the plate preparation. The above ratio may be the ratio of the length of the plate preparation and the circumference, in particular of the middle, plate preparation, in which the above circumference may, for example, be twice the width of the plate preparation if the plate preparation is in the form of a strip.

In particular, this has an advantage when applied to the mucosa. More specifically, the mucous membrane of the esophagus may be coated with such a flat preparation, and / or topical treatment with such a flat preparation containing the active pharmaceutical ingredient may be applied to it. It should be understood that, depending on the particular embodiment of the dosage form, the plate preparation may, at least partially and preferably to a sufficiently large size, cover the mucous membrane of the esophagus and / or may increase, at least partially and preferably to a sufficiently large length, along the longitudinal axis of the esophagus. Thus, in a preferred embodiment, the active pharmaceutical ingredient can be released into the enlarged portion of the mucous membrane of the esophagus, whereby such an expanded portion can be treated. Moreover, in an alternative or preferred embodiment with a lamellar preparation which does not dissolve immediately, but preferably dissolves in a time-controlled manner and / or adheres to the mucous membrane, the active pharmaceutical ingredient may be released after some time, due to which, in particular, the effectiveness of the therapeutic treatment may be increased.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the release mechanism is an expansion mechanism, preferably a stretching mechanism, configured to increase the plate preparation by efficiently utilizing external movement, force or pressure.

It should be understood that external movement, force, or pressure, in particular, may be present at a predetermined starting point, place of application, or place of exposure. Thus, it can also serve as a key stimulus for the trigger mechanism. Additionally or alternatively, external movement, force, or pressure may increase the plate preparation along with the release mechanism. In this context, external movement, force, or pressure refers to movement, force, or pressure that is external to the pharmaceutical dosage form. Preferably, the aforementioned movement, force, or pressure is produced, at least in part, by the human or animal body into which the pharmaceutical dosage form is administered, and thus is not external to the aforementioned organism. Thus, such a movement may be, in particular, a passive movement. Preferably, such external movement is the movement of the mucous membrane, the movement of fluids that are present at a predetermined launch site, place of application or place of exposure, movement of muscles, in particular muscles that are located close to the organ with the corresponding mucous membrane or belong to this organ, peristaltic movement or swallowing movement. In particular, the dosage form or part thereof may preferably passively move relative to the user's body, in particular relative to the mucous membrane or organ. Preferably, such an external force can be caused by the above external movements or represents the force generated by the fluid surrounding the dosage form, the force generated by the mucous membrane, which, in particular, is in contact with the pharmaceutical dosage form or part thereof, the force generated by the muscles that are located close to the organ with the corresponding mucous membrane or belong to this organ. Preferably and in a similar way, such external pressure may be caused by the above external movements or may be the pressure of the fluid surrounding the pharmaceutical dosage form, in particular, created by the corresponding mucous membrane or the corresponding muscles, in particular, the wall of the gastrointestinal tract. It should be understood that gravity can additionally act on the dosage form or part thereof, which can enhance, increase, lower, restrain or develop the above movement, force or pressure. More specifically, the buoyancy force can be considered an external force and / or can be used to increase the plate preparation.

More specifically, in the case of oral administration of the dosage form, preferably for use in relation to the esophagus, the external movement may be the movement of the dosage form when swallowed. Thus, the muscles of the esophagus create a force that acts on the dosage form or part thereof. In particular, the mucous membrane of the esophagus can act directly on the dosage form and / or can indirectly act on the dosage form, preferably by means of a liquid, in particular, such as a drink, water or saliva, which was preferably swallowed together with the dosage form. Due to such movements, force or pressure can occur. From another point of view, the above movements can cause forces and / or pressure of the esophagus, its mucous membrane and muscles. In particular, a change in the pressure of the swallowed liquid can be used as a key stimulus for the trigger mechanism. Thus, the increase in the plate preparation can be improved, and / or the release mechanism can be simplified. Preferably, the release mechanism can release the plate preparation for the most part passively; thus, an increase in the plate preparation occurs without the development of additional strength from the pharmaceutical dosage form. Thus, an active release mechanism containing an energy source, for example, a gas generating substance or a spring, is not required, or at least the energy requirements for the release mechanism, which only partially contributes to passive expansion, are reduced. In addition, this preferred embodiment, in particular, allows the release of the plate preparation upon ingestion of the dosage form. Finally, manufacturing costs can be reduced and safety, user friendliness and / or reliability can be enhanced.

An advantage of the preferred embodiment, which allows the effective use of external movement, force or pressure, can consist, in particular, in reducing the risk of injury when using a pharmaceutical dosage form and in increasing safety and convenience for the user, and / or in reducing production costs. Preferably, the risk of injury can be reduced, since the movement, force or pressure necessary to increase the plate preparation is external and thus is not created by the dosage form, but, in particular, by the body of the user himself. Additionally or alternatively, manufacturing can also be simplified, since the release mechanism, preferably the expansion mechanism, does not have to create a force, movement or pressure on its own, but only use external force, movement or pressure, as a result of which additional appropriate structures and / or parts can be dispensed with .

Additionally or alternatively, the effective use of movement, force or pressure to expand the plate preparation can be successfully combined with the release of the plate preparation during movement along the mucous membrane. In particular, such a combination can release the lamellar preparation, at least partially, along its path of movement, and this release can be facilitated, or such release can be fully realized by using just such a movement. In this way, manufacturing can be simplified, costs reduced, and safety, user friendliness, and reliability can be enhanced. In an advantageous embodiment of the pharmaceutical dosage form of the present invention, the release mechanism and / or trigger mechanism may be formed, at least in part, by a plate preparation. This allows to simplify the design and / or manufacture. In particular, manufacturing costs can be reduced. Preferably, the reliability of the pharmaceutical dosage form can be improved, in particular by reducing the number of components.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the pharmaceutical dosage form, in particular the shell, comprises a lamellar preparation in a compact form, preferably in a folded, compressed, rolled up, rolled or rolled up form, and the release of the lamellar preparation due to the release mechanism, in particular , the expansion mechanism, leads to the deployment, unwinding, stretching or stretching of the plate preparation, in particular, to the expanded form. This, in particular, provides the advantages described above regarding compact and / or expanded form. In particular, elongation along an axis or a trajectory of movement, preferably along the longitudinal axis of the lamellar preparation in its expanded form, mainly allows the active pharmaceutical ingredient to be released over an extended section of the mucous membrane, as well as in a small dosage form compared to the above extended section, and, as a result , with preferably oral administration of the dosage form.

In a preferred embodiment of the dosage form of the present invention, the trigger mechanism is a holding device that is part of or attached to the plate preparation. In particular, it is useful to maintain in a fixed position at least a portion, preferably an end, of the plate preparation and / or the sectional element while other parts of the plate preparation or dosage form are in motion. Preferably, the holding device is configured to fix it, in particular to attach, install or secure, in a predetermined area or part of the user's body, or in a predetermined position. Moreover, the force acting on the restraint may serve as a key incentive. Especially, such a force acting on the holding device can be caused by external movement, force or pressure that acts on the pharmaceutical dosage form. It should be understood that the holding device may also not be attached to the plate preparation directly. In particular, a plate preparation can transmit power to a holding device, and vice versa, with the help of another part of the pharmaceutical dosage form. In particular, it should be understood that the holding device may be formed by a sectional element or part thereof.

In a preferred embodiment, the dosage form of the present invention, in particular the oral dosage form, the trigger mechanism, in particular the holding device, is configured to fix it in the oral cavity, preferably on the teeth, on the tongue, on the lips or on the mucous membrane the oral cavity. Additionally or alternatively, the trigger mechanism is configured to hold it in the hand, preferably by the user, while swallowing the pharmaceutical dosage form.

In particular, this advantageously provides the desired position of the trigger mechanism, preferably the holding device, especially during the administration, for example, swallowing, of the pharmaceutical dosage form. Preferably, in this way, the position of the trigger mechanism, in particular the holding device, can be predefined for use. Preferably and alternatively, the position of the trigger mechanism may be the result of arbitrary attachment, in particular, to the site of the corresponding mucous membrane. More specifically, the trigger mechanism, preferably the holding device, can have adhesive properties and then, prior to swallowing the pharmaceutical dosage form, can be arbitrarily attached to the mucous membrane of the cheek or tongue. This, in particular, provides an advantage, since the user can simply put the pharmaceutical dosage form in his mouth and then, preferably with a liquid, swallow it, while the trigger mechanism, preferably the holding device, can be attached in the oral cavity without further and / or special action user.

The term "holding device", as used in the present description, preferably refers to a device that is configured to hold itself and, optionally, additional parts that are attached to it, for example, parts of a plate preparation, in a certain position. In particular, the holding device is a handle, loop or adhesive tape or comprises an adhesive area. Moreover, the holding device can be configured to form and maintain a connection that can transmit power between the holding device and the portion to which it is attached. In addition, this relationship can be formed or can be maintained when the dosage form and / or plate preparation are in their compact form and / or in expanded form. Preferably, the holding device can hold itself and possibly additional parts in a certain position or in a certain area due to tight fit, in particular due to friction, conforming to the shape or adhesion of the material, in particular due to mucoadhesive, preferably adhesive bonding .

An advantage of such a holding device may arise from the fact that the force acting on the pharmaceutical dosage form and / or the movement of the pharmaceutical dosage form can be used as a key stimulus for the trigger mechanism, where preferably the holding device is a trigger mechanism or part thereof to trigger release of the plate preparation. Preferably, in the embodiment of the present invention, the holding device can advantageously be combined using external movement, pressure or force to expand the plate preparation. In particular, external movement and / or force can serve as a key incentive for the trigger mechanism, wherein the trigger mechanism preferably triggers the release of the plate preparation by the release mechanism, and then the above external movement, force or external pressure can be used to expand the plate preparation, preferably by a mechanism release. In particular, this is possible in the case where the dosage form of the present invention is passively moving relative to the position in which the holding device is fixed. In addition, the holding device and / or the effective use of external movement, force or pressure can preferably be combined with the release of the plate preparation during the movement of the dosage form or part thereof along the mucous membrane. In this case, a controlled and / or directed start of the release can be achieved, the release and / or contact of the lamellar preparation at the desired mucosal area can be achieved and / or through the use of external movement, force or pressure, the release mechanism can be simplified, the release mechanism can be reduced manufacturing costs, and user convenience and security can be enhanced.

In some embodiments, the convenience for the user may increase the fixation of the holding device in the oral cavity. In addition, the holding device, which is made with the possibility of fixation in the oral cavity, can be manufactured in a simple and, therefore, economical way, and / or can be especially reliable, including due to the fact that the user can check whether it is properly fixed a holding device before continuing to administer the dosage form, for example, before swallowing the dosage form or part thereof. A holding device that is capable of being held in the hand during administration of the dosage form may have similar advantages.

In a preferred embodiment, the pharmaceutical dosage form of the present invention, at least during the release of the plate preparation, the released portion of the plate preparation and the pharmaceutical dosage form move relative to each other and thus determine the trajectory of the dosage form. In addition, when observing in the direction of the trajectory of movement, the envelope surface of the cross section of the dosage form is larger than the envelope surface of the plate preparation. In particular, the envelope surface of the cross section of the dosage form may refer to the envelope surface of the cross section of the swallowed portion of the dosage form, preferably the shell. In particular, the envelope surface of the cross section of the plate preparation may refer to the envelope surface of the released portion of the plate preparation. It should be understood that these relationships, in particular, take place during the release of the plate preparation. In particular, the plate preparation may increase, as a result of which it may subsequently have a larger envelope surface of the cross section than the dosage form. It should be understood that the relationships described above are especially important for a portion of a plate preparation that has already been released in a dosage form. Preferably, the length of such a portion, measured along the path of movement, is at least substantially equal to the length of the dosage form, measured along the path of movement, preferably two times longer, preferably five times longer and preferably twenty times longer. In particular, the ratio of the surface envelopes of the cross-sections can be expressed in relation to and / or can correspond to the ratio of the corresponding maximum or minimum diameters, which can repeat the corresponding transverse axes or can be located at least almost orthogonally to the corresponding longitudinal axes or direction of movement.

This can advantageously provide simplification of the movement of the dosage form due to swallowing or peristaltic movements. Specific embodiments of this embodiment may increase user convenience and / or reduce the risk of injury. In particular, since at least a portion of the released plate preparation that follows the dosage form has a smaller cross-sectional area, such a dosage form is better swallowed. More specifically, the narrowing at the back of the dosage form helps the musculature of the esophagus to swallow the dosage form. Preferably, the dosage form, in particular the shell, such as a capsule, also tapers towards one end, at least in the direction and / or against the direction of the predetermined path of movement, and thereby further facilitates swallowing. In addition, the dosage form may be configured such that the longitudinal axis is at least substantially parallel to a predetermined path of movement. Moreover, the dosage form can release the plate preparation against the direction of a predetermined motion path, for example, at the rear of the dosage form relative to a predetermined motion path or motion of the dosage form.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the plate preparation contains at least a first portion and a second portion with different envelope surfaces of the cross section, in particular when observed in the direction of the path of movement, where the portion released earlier than the other portion has a smaller cross-sectional area. In an alternative or preferred embodiment, the lamellar preparation tapers from the second end of the lamellar preparation to the first end of the lamellar preparation, where the first end of the lamellar preparation is located on the side of the lamellar preparation that is released first. In particular, for use in relation to the esophagus, both options result in a lamellar preparation, which after its release is smaller in the upper region of the esophagus and oral cavity and more in the lower region of the esophagus. This can advantageously facilitate swallowing of the dosage form and / or increase user convenience, in particular, suppressing the emetic reflex or avoiding it. In a preferred embodiment, the first portion is a sectional element.

It should be understood that the terms "pharmaceutical dosage form" and "dosage form" are used interchangeably. Preferably, the dosage form may be of non-medicinal use. In particular, the dosage form can be used to treat and / or diagnose a disease.

It should be understood that some embodiments of the pharmaceutical dosage form of the present invention differ from the catheter in that they, at least almost completely, are enclosed in the user's body after administration. Additionally or alternatively, the introduction is carried out without additional tools and / or without the use of effort or movement that is external to the user's body. Preferably, the pharmaceutical dosage form in accordance with the present invention can be entered by the user without professional assistance. This, in particular, is useful if the dosage form must be administered regularly, in particular daily. In addition, convenience and safety can be enhanced, and / or the risk of injury to the user can be reduced. In particular, convenient administration is also useful for treating animals. It should also be understood that the pharmaceutical dosage form of the present invention is different from the stent. In particular, the stent, as a rule, does not contain a trigger mechanism in the sense of the present invention. Moreover, the goal of most stents is to keep the hollow organ open. Some embodiments of the pharmaceutical dosage form of the present invention can also support the hollow organ in the open state, however, in addition to the goal of maintaining the hollow organ in the open state, the goal of such options is at least to improve the local use of the drug, in particular , active pharmaceutical ingredient. Some other embodiments of the pharmaceutical dosage form of the present invention are aimed at improving the local application of the drug, in particular the active pharmaceutical ingredient, and allowing the closure of the hollow organ, in particular even during the use of the dosage form. In particular, this can be achieved using a pharmaceutical dosage form containing a sectional element or plate preparation, which, in particular, in expanded form, is formed in the form of a section, cord, strip or tube. In particular, it is especially suitable for the treatment of the esophagus.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the pharmaceutical dosage form, in particular the shell, comprises at least one opening and is configured to release the plate preparation as it passes through the at least one opening. A preferred embodiment provides the advantage of protecting the plate preparation by keeping it in the shell. In addition, the reliability of a dosage form releasing a plate preparation through an opening can be improved. Additionally or alternatively, administration can be improved, in particular, user convenience can be enhanced, due to the fact that the hole allows for controlled and / or directed release of the plate preparation.

In a preferred embodiment of the present invention, the pharmaceutical dosage form comprises at least one hole, where the trigger mechanism and the plate preparation are located at least partially on opposite sides of the at least one hole. Preferably, the trigger mechanism is not included, or only partially contained in the shell of the dosage form. Preferably, the plate preparation, at least in part, is contained in a dosage form shell. This may increase the reliability of the pharmaceutical dosage form and / or user convenience. In particular, storage stability can be improved. In addition, this allows you to trigger the trigger mechanism using a key stimulus, which is external to the dosage form and should not enter the inner part of the dosage form, in particular, in the shell of the dosage form. Moreover, the trigger mechanism may be exposed to the external environment and thus be more sensitive to a possible key stimulus. Preferably, the trigger mechanism may comprise or be a restraint that can be exposed to and / or fixed in the oral cavity, or that can be held in the hand.

In a preferred embodiment of the pharmaceutical dosage form of the present invention, the release mechanism comprises or is an unwinding device that is configured to release the plate preparation by unwinding it. This can advantageously ensure the release of the plate preparation, which in its compact form is twisted, rolled up or wound. Moreover, such an unwinding device can be conveniently formed by a flat preparation or part thereof by forming a spiral. Preferably, such a spiral can be held on a rod, which can improve the possibility of its unwinding.

In some embodiments of the pharmaceutical dosage form of the present invention, the lamellar preparation is in a solid state, in particular while it is in compact form and / or immediately after its release. This can successfully enhance, make possible, or develop some of the above benefits. In particular, if the plate preparation is in solid form prior to release, this may increase its storage stability. In particular, if the lamellar preparation is in a solid state after release, this can increase and / or provide targeted and / or sustained release of the active pharmaceutical ingredient. Additionally or alternatively, in specific embodiments of the pharmaceutical dosage form of the present invention, the platelet preparation may be capable of dissolving after release, for example, biodegradable, immediately, with a delay, time-controlled manner or as a result of exposure to a stimulus. This can successfully enhance, make possible, or develop some of the above benefits. In particular, this can enhance user convenience, since the plate preparation does not require removal.

All embodiments of the pharmaceutical dosage form of the present invention demonstrate the advantage that a pharmaceutical dosage form is provided in which the bioavailability of the active pharmaceutical ingredients that contains the administered dosage form is increased, or in which, in particular, the local effect of the active is enhanced or alternatively pharmaceutical ingredient. Additionally, using the pharmaceutical dosage form of the present invention, the release of the active pharmaceutical ingredient at a predetermined site of exposure is improved. Other advantages of the pharmaceutical dosage form embodied by the present invention are as follows:

- Equal effect achieved when using a lower dose

- Reduction of side effects due to a lower dose

- Fast onset of action due to direct contact with the place of use.

Brief Description of the Drawings

Examples of embodiments of the present invention are described below in more detail with reference to the relevant drawings and examples, from which you can understand additional characteristics, advantages and options for implementation.

In FIG. 1 is a schematic illustration of a general view of a pharmaceutical dosage form of the present invention in accordance with a first embodiment, in an initial state;

In FIG. 2 is a schematic representation of a general view of a pharmaceutical dosage form of the present invention in accordance with a first embodiment in a state after release of a plate preparation by a release mechanism;

In FIG. 3 is a schematic illustration of a general view of a pharmaceutical dosage form of the present invention in accordance with a second embodiment, in an initial state;

In FIG. 4 is a schematic representation of a general view of a pharmaceutical dosage form of the present invention in accordance with a second embodiment, in a state after release of a plate preparation by a release mechanism;

In FIG. 5a, 5b are a schematic illustration of a general view of a pharmaceutical dosage form of the present invention in accordance with a third embodiment, in an initial state;

In FIG. 5c is a photograph of a pharmaceutical dosage form of the present invention in accordance with a third embodiment, in an initial state;

In FIG. 6a, 6b are a schematic representation of a general view of a pharmaceutical dosage form of the present invention in accordance with a fourth embodiment, in an initial state;

In FIG. 6c is a photograph of a pharmaceutical dosage form of the present invention in accordance with a fourth embodiment, in an initial state;

In FIG. 7 shows a schematic structure of a sample of a three-layer film preparation of the present invention;

In FIG. 8a, 8b are a schematic illustration of a general view of a pharmaceutical dosage form of the present invention in accordance with a fourth embodiment; and

In FIG. 8c, envelopes of the cross-sectional surfaces of the fourth embodiment of the present invention are illustrated.

The implementation of the invention

In FIG. 1 is a schematic representation of a general view of a pharmaceutical dosage form 1 of the present invention in accordance with a first embodiment, in an initial state. In FIG. 2 shows the pharmaceutical dosage form 1 of FIG. 1 in the post-release state of the plate preparation 3 by the release mechanism 4. In FIG. 1 and 2, it can be seen that the depicted pharmaceutical dosage form 1 contains, in particular, for oral administration, a shell 2 made in the form of a capsule; the shell contains a lamellar, in particular, film, foil or wrapper preparation 3, containing the active pharmaceutical ingredient in the form of a folded and accordingly folding cachet 3, as well as a release mechanism 4 and a trigger mechanism 5, which is configured to trigger the release of the plate preparation 3 using the mechanism release 4 at a predetermined site of exposure, in particular in the gastrointestinal tract. The shell 2 of the dosage form 1 contains an opening 6a on one side, and an opening 6b on the opposite side, in particular, the opening 6b can be formed as a slot. The hole 6a is covered by the trigger mechanism 5. When this hole at the point of exposure is in contact with the liquid surrounding the dosage form, then it dissolves and the liquid can come into contact with the interior 7 of the shell 2. The hole 6a is at least partially covered by the trigger mechanism 5 for example, a soluble polymer, which is configured to trigger the release of the plate preparation 3 using the release mechanism 4 after contact of the pharmaceutical dosage form 1, in particular, trigger a mechanism 5, a key driver. Thus, a predetermined change in the physical or chemical parameter or fluid surrounding dosage form 1, in particular, gastric juice in the stomach or, alternatively, also small intestine fluid, which has a significantly lower pH compared to the pH of the oral cavity and the pharyngeal cavity, serves as a key stimulus for actuating the trigger mechanism 5. The trigger mechanism 5 is made of a substance whose solubility and strength depend on the pH in the stomach.

In FIG. 2, the trigger mechanism is no longer shown because it has already dissolved. Shell 2 is made of a material that is practically insoluble in gastric juice, for example, hard gelatin or starch, which is additionally coated with other polymers that are stable in themselves (for example, eudragit and others) to maintain stability in the gastric juice. The release mechanism 4 is designed as an expansion mechanism that contains a wick system, more specifically a gas expansion system, to which liquid enters through the wick system due to capillary forces. An increase in the expansion mechanism may lead to the opening of the shell 2 at a predetermined location of the gap 8 or, alternatively, suitable for the destruction of the coating, the sealing hole 6b. This coating in the initial state protects the dosage form 1 from unwanted liquid penetration through the opening 6b. The latter can be seen in conjunction with FIG. 1 and FIG. 2. The preparation 3 is contained in the shell 2 when folded, as shown in FIG. 1, wherein, as shown in FIG. 2, the expansion of the mechanism leads to the unfolding of the drug 3, while the drug 3 exits through the slot 6b and swells like a balloon. To this end, in the region of the shell 2, which is shown in FIG. 1 and FIG. 2 on the left, in the form of a release mechanism 4 (or an expansion mechanism), a gas-forming substance, for example, a powder, which can be selectively incorporated into a wick system, in particular containing capillaries, for example, fibers that can absorb liquid, is contained. For example, in this case, sodium bicarbonate or citric acid, or alternatively compressed gas, are suitable as a gas-forming substance.

In particular, the release mechanism and the expansion mechanism are formed in such a way that the gas to be formed is directed only to the plate or cylinder 3 and does not exit elsewhere. During release, the powdery gas generating agent and the wick system 4 maintain contact. As a consequence, it is advisable if the gas generating substance is incorporated into the wick system.

In the case of a liquid or partially liquid blowing agent, the blowing agent may be contained in a separate compartment, which is at least partially formed from the outer shell 2 of the dosage form. Thus, the gas-generating substance is located in the part of the shell 2, which is opposite to the other part of the shell containing the preparation 3 and located on the right side of the shell in the images. The gas-resistant shell, which can be filled with gas, has a central hole 6a, which is attached around the circumference on the inner edge of the shell 2. After activating the release mechanism, the liquid enters the release mechanism in the form of a gas-forming substance through the wick system, and the gas-forming substance forms gas, which enters the interior of the plate preparation 3. For this purpose, the preparation is formed in the form of a gas-resistant shell, which can be filled with gas, in particular, in the form bottle, as shown in particular in FIG. 2.

In FIG. 1 preparation 3, formed in the form of a gas-resistant, gas-filled shell is presented in folded form. In addition, from FIG. 1 you can see that the shell is divided along the contour. From FIG. 1, it can also be seen that the shell contains at least one predetermined break point. It should be understood that, depending on the actual embodiment, it may be sufficient for the balloon 3 to exit only through the slot 6b. However, further experiments showed that, for the balloon to fully unfold, the predetermined gap point 8 on the shell 2 can completely collapse or open, in particular, due to the pressure of the gas created in the balloon 3. In particular, such a mechanism can be held together by coating the slot 6b in initial condition. Such a coating can also be selected in such a way that, in particular, when it is selected from the same or the same material as the trigger mechanism 5, such a coating is destroyed or dissolved at the launch site or at the site of exposure, so that the gas pressure can open the capsule 2. For this purpose, it may be advisable that the coating of the slit 6b dissolves more slowly than the trigger mechanism 5. It should be understood that in various actual additional embodiments, only one predetermined one is possible 8 ECTA rupture or folding mechanism in this position, or perhaps only the presence of the slit 6b, or combinations of these elements. The actual embodiment may be selected by a person skilled in the art depending on the size and scope of application and depending on the materials actually used.

Gastric juice or intestinal fluid enters through the opening 6a into the inner space 7 of the membrane at a predetermined launch site, in this case, for example, in the stomach or intestines, and leads to the formation of gas by the gas generating substance. At the same time, the gas enters the internal space of the plate 3, which at a predetermined location of use is inflated like a balloon and increases in volume. At the same time, the shell 2, made in the form of a capsule, opens at one end — in this case, on the right — due to, for example, a gap in a predetermined gap 8 under the influence of the pressure of an increasing balloon 3 and / or due to the exit of the balloon 3 through the opening 6b . As a result of this, the cachet preparation 3 can be fully unfolded and released from capsule 2. In particular, this design allows the formation of a relatively large folded surface that can be located on a relatively large area of the wall of the stomach to release the active pharmaceutical ingredient. Alternatively, and in particular, this design allows the formation of a relatively large folded surface, which can be located on a relatively large area of the intestinal wall to release the active pharmaceutical ingredient. It should also be understood that part of the wick system 4 may protrude from the shell and direct fluid into the interior of the shell 2. It is advisable to cover the part of the wick system 4 that is located outside the shell in the initial state to be released after activation.

In FIG. 3 is a schematic illustration of a pharmaceutical dosage form 1 of the present invention in accordance with a second embodiment, in an initial state. As in the previous case, the pharmaceutical dosage form 1, which is particularly suitable for oral use, contains a shell 2, where the shell 2 contains a lamellar, in particular film, foil or wrapping preparation 3 containing the active pharmaceutical ingredient in the form of a folded cachet 3 as well as the release mechanism 4 and the trigger mechanism 5, which is configured to trigger the release of the cachet 3 due to the release mechanism 4 at a predetermined site of exposure, for example, in the intestine. The shell 2 has central openings 6a and 6b, respectively, on both sides, which are covered by a coating, for example, an insoluble or similar coating. After application, the openings 6a and 6b become closed, whereby the trigger mechanism 5 may come into contact with the liquid. However, the opening does not have to be present, since the trigger mechanism can also be located on the circumference of dosage form 1. After dissolving the coating, the fluid of the gastrointestinal tract or small intestine surrounding the membrane 2 comes into contact with the inner space 7 of the membrane. The trigger mechanism 5 is configured to trigger the release of the plate preparation 3 by the release mechanism after the pharmaceutical dosage form, in particular the trigger mechanism 5, comes in contact with a key stimulus. For example, in the depicted embodiment, the key stimulus is the effect of pressure caused by intestinal motility or a specific pH value, usually prevailing or occurring at the site of exposure. In the depicted embodiment, the trigger mechanism is formed using a soluble polymer, which is located inside the tubular elements 11 and 12. In particular, the pressure can serve as a key effect if the capsule arms are held together by a material that collapses under pressure. The release mechanism 4 is designed as an expansion mechanism, and specifically as a mechanical expansion system, in which an increase in the expansion mechanism leads to the deployment of the cachet 3.

In FIG. 4 shows the embodiment depicted in FIG. 3, in the expanded state. The shown embodiment comprises, as part of a mechanical expansion system, several connecting or lever elements 13, which are located at both free ends of the shell 2 in the region of the central hole 6, as well as a spring element 10, which is located inside the tubular elements 11 and 12, which are each to a friend. In particular, the connecting or lever elements 13a of the first tube 11 and the connecting or lever elements 13b in the tube 12 are alternately in the closed initial state of the dosage form 1, as shown in FIG. 3, so that in the closed state, as shown in FIG. 3, the connecting or lever elements 13a of the first tube 11 and the connecting or lever elements 13b of the second tube form a shell 2 or coating, which, when released, opens by clicking and opens the preparation 3.

In particular, the length of the lever of the connecting or lever elements 13a of the first tube 11 and the connecting or lever elements 13b of the second tube 12 is equal to the total length of the folded dosage form 1 in this arrangement. It should be understood that in the case where the lever or connecting elements 13a and 13b are located opposite each other, the maximum length of the lever is limited to half the length of the dosage form 1. In this case, the first and second tubular elements 11 and 12, as well as the lever and connecting elements 13a and 13b are arranged so that the lever and / or connecting elements 13a or 13b form a spiral structure, and the lever and connecting elements 13a in the tubular element 11 and the lever and connecting elements 13b in the tubular element 12, respectively, laid in the slots in the tubular element 11 or 12, if you look at the dosage form 1 from the front or the front and thus see the smallest surface area of the dosage form 1. The elastic force of the spring 10 pushes the lever and connecting elements 13a and 13b through the slot 16 to the outside, and the plate 3 expands as the cover or shell elements 17, which are pivotally attached to the linkage or connecting members 13a and 13b, open outward. In this context, it should be understood that pivotally attached elements 17 of the coating or shell can also form a lever or connecting elements and can be understood as such.

In such an arrangement, it is advisable that, as shown in FIG. 3, in the closed state of the dosage form 1, the coating or shell elements 17 of the first tube 11 forming the connecting or lever elements, and the coating or shell elements 17 of the second tube 12 forming the connecting or lever elements are arranged alternately so that in the closed state the elements 17 the coatings or shells of the first tube 11 forming the connecting or lever elements, and the coating elements 17 or the shells of the second tube 12 forming the connecting or lever elements preferably formed the shell y and / or coating 2. The spiral structure at the first end of dosage form 1, in particular at the end of the first tubular element 11, and the spiral structure at the second end of dosage form 1, in particular at the end of the second tubular element 12, are balanced by rotationally symmetric way. The butt or lever movement of the connecting elements 13a and 13b causes the plate preparation 3 to unfold, which is folded in the initial state in the dosage form 1, due to the outward movement in the slot 16, due to the compression force of the spring, since the coating or sheath elements 17 open outward, so that the plate the preparation 3 unfolds at a predetermined site of exposure in a particular advantageous manner and preferably can come into contact with the mucous membrane of the intestinal wall.

The shell 2 contains tubular elements 11 and 12, which are pressed into each other by a spring 16 located in the tubular elements 11 and 12 so that they can move relative to each other and are located centrally on the main longitudinal axis of the dosage form 1. Due to the action of peristalsis pressure intestines or dissolution of the coating and a significant flow of fluid into the trigger mechanism or release mechanism, the mechanical expansion system is activated, and due to the connecting or lever elements 13a, 13b, triggered spring, in combination with the elements 17 of the coating or shell, the deployment of the plate 3 and, therefore, its release from the shell. In particular, such an increase can be facilitated or controlled by providing at least an additional connecting or lever member.

In FIG. 5a and 5b are a schematic illustration of a pharmaceutical dosage form 1 of the present invention in accordance with a third embodiment, in an initial state, and FIG. 5, a photograph of a pharmaceutical dosage form of the present invention in accordance with a third embodiment is shown in an initial state. In FIG. 5a is a side view, and FIG. 5b is a tip view. Such a pharmaceutical dosage form 1 of the present invention is made with the possibility of introducing on the mucous membrane, in particular on the mucous membrane of the vagina, as well as on the mucous membrane of the rectum, and contains a lamellar, in particular film, foil or preparation 3, which contains an active pharmaceutical ingredient in the form of a cachet, which is located around the circumference in a longitudinal section of a cylindrical main body of a dosage form 1, which tapers at one end. In particular, the main body may be a tampon, which is mainly formed from a material capable of swelling. A swellable material can form both a release mechanism 4 and a trigger mechanism 5, which swells as a result of contact of dosage form 1 with a liquid, in particular with a vaginal fluid, and thereby expands the preparation 3. Due to the increase in the diameter of the dosage form 1 due to swelling, the circumference of the drug 3 also increases. This happens because the preparation 3 can be laid in the grooves or indentations of the main body of the dosage form.

In FIG. 6a, 6b and 6c show alternative embodiments that differ from the embodiment shown in FIG. 5a, 5b, 5c in that in this case the preparation 3 is partially placed outside. Due to the swelling of the main body of the dosage form at a predetermined site of exposure, in this case, in particular, in the rectum or, preferably, in the vagina, the release of the plate preparation 3 is triggered by the release mechanism 4.

It should be understood that the main body of the dosage form 1 may or may not contain grooves, depending on the embodiment.

In particular, however, the polymer can serve as an additional trigger mechanism 5 as an adhesive, where after contact with the liquid at the launch site the polymer is at least partially or completely dissolved. In particular, such a polymer can fix the preparation 3 on the main body or can additionally or alternatively glue the folds of the cachets 3 together. In particular, this can lead to the fact that the wafer 3 does not unfold, since the polymer, acting as a trigger mechanism 5, has not completely dissolved, or at least partially. In the context of the embodiments depicted in FIG. 5 and FIG. 6, it should also be understood that they are, in particular, suitable for variants where rapid and immediate release and dissolution are provided and, as a result, the relatively quick and immediate contact of the cachet preparation with the place of use, in particular with the vaginal mucosa.

In FIG. 7 shows a schematic structure of a three-layer plate preparation. A plate preparation, for example, containing a pharmaceutical dosage form 1 of the present invention, may have a thickness of from 0.01 mm to 2 mm, preferably from 0.03 mm to 1 mm, preferably from 0.05 mm to 0.1 mm, the plate preparation 3 has an area of from 0.5 to 20 cm ² , preferably from 1 to 10 cm ² . In particular, the lamellar preparation 3 contains at least one layer containing the active pharmaceutical ingredient. The lamellar, in particular film, foil or wrapping preparation 3, which preferably has the form of a wound, contains the active pharmaceutical ingredient with an active ingredient content of from 0.5 to 40 wt.%, Preferably from 1 to 30 wt.%, Most preferably from 5 to 20 wt.%. The plate preparation 3 may have a single layer or multilayer structure consisting of one or more layers 9, in which at least one first layer 9a contains an active pharmaceutical ingredient. In FIG. 7 shows an example of the structure of a three-layer cachet 3, in which only one layer contains the active substance 9a.

Further explanations of the dosage form of the present invention are given in the following examples.

Example 1

The single-layer or multi-layer preparation of the present invention preferably has a leaf shape.

The preparation of the present invention dissolves preferably within 1 hour, more preferably within 30 minutes, most preferably within 15 minutes and, in particular, most preferably within 5 minutes after contact with the site of exposure, in particular with the mucous membrane.

The plate preparation preferably contains a mucoadhesive layer containing the active substance, which mainly contains: mucoadhesive polymers such as cellulose derivatives, starch and starch derivatives, polyvinyl alcohol, polyethylene oxide, polyethylene, polypropylene, polyacrylic acid and polyacrylic derivatives, polyvinylpyrrolidone, sodium povidone alginate, gelatin, xanthan gum, guar gum, carrageenan, pectins, dextrans, lectins, chitosan, pullulan, as well as mixtures of these substances; plasticizers, such as polyethylene glycol, glycerol, sorbitol, as well as mixtures of these substances; solvents such as water, ethanol, methanol, acetone, organic solvents, as well as mixtures of these substances. In addition, excipients such as colorants, flavors, flavors, preservatives, antioxidants, absorption enhancers, solvents, decomposition accelerators, lubricants and mixtures of such substances may be included.

In particular, substances from the following groups are suitable as active pharmaceutical ingredients: drugs acting on the skeleton and muscles, drugs acting on the nervous system, hormones and drugs acting on the hormonal system, drugs that have a gynecological effect, drugs acting on the cardiovascular system, drugs acting on the respiratory system, drugs acting on the gastrointestinal - intestinal tract, diuretics, drugs acting on the sensory organs, cutaneous preparations, vitamins and minerals, peptide drugs and proteins, analgesics, anti-infective and antiparasitic drugs.

Development and testing

In order to develop and test the drug in the form of a cachet suitable for the present invention, test methods based on the following test and selection protocol 1 are implemented.

Thus, preparations are obtained that meet the requirements that arise, in particular, for use for the dosage form. In particular, the wafers of the present invention differ from previously known wafers in that they do not dissolve already with little contact with the liquid and that they have a relatively high ductility and fracture resistance.

Test and selection protocol 1

Film composition development

In particular, for the mucous membrane of the vagina, rectum or intestines, to increase safety, user convenience and / or to ensure a tight but flexible fit of the plate preparation on the corresponding mucous membrane, the recommended tensile strength may be less than 3.5 MPa.

In particular, for the mucous membrane of the esophagus and / or for use in relation to the esophagus, it may be advisable to have a tensile strength of less than 15 MPa, in particular, in order to avoid destruction of the plate preparation during its use, especially during swallowing of the dosage form.

Example 2 - Single Layer Preparation

Single-layer preparations, in particular cachets, suitable for use in the present invention may have the following compositions:

A 10% PVA

20% PEG 400

5% HPMC

x% active pharmaceutical ingredient

up to 100% demineralized water

In 5% PVA

15% Kollicoat ^® IR (collicoat IR)

x% active pharmaceutical ingredient

up to 100% demineralized water

or

With 5% PVA

15% Kollicoat ^® IR (collicoat IR)

8% glycerol 85%

x% active pharmaceutical ingredient

up to 100% demineralized water

Example 3 - Bilayer preparations

The bilayer preparations, in particular cachets, of the present invention comprise a mucoadhesive layer containing the active substance and a waterproof layer, which is called a coating layer. The mucoadhesive layer containing the active substance preferably consists of mucoadhesive polymers such as cellulose derivatives, starch and starch derivatives, polyvinyl alcohol, polyethylene oxide, polyethylene, polypropylene, polyacrylic acid and polyacrylate derivatives, polyvinylpyrrolidone, povidone, copovidanine, sodium gum, guar gum, carrageenan, pectins, dextrans, lectins, chitosan, pullulan, as well as mixtures of these substances; plasticizers, such as polyethylene glycol, glycerol, sorbitol, as well as mixtures of these substances; solvents such as water, ethanol, methanol, acetone, organic solvents, as well as mixtures of these substances. In addition, excipients such as colorants, flavors, flavors, preservatives, antioxidants, absorption enhancers, solvents, decomposition accelerators, lubricants and mixtures of such substances may be included. Substances from the following group are suitable as active pharmaceutical ingredients: drugs that act on the skeleton and muscles, drugs that act on the nervous system, hormones and drugs that affect the hormonal system, drugs that have a gynecological effect, drugs that act on cardiovascular system, drugs acting on the respiratory system, drugs acting on the gastrointestinal t act, diuretics, drugs that act on the sense organs, transdermal preparations, vitamins and minerals, peptide drugs and proteins, analgesics, anti-infective and anti-parasitic drugs.

The coating layer preferably contains a layer of ethyl cellulose of various thicknesses, in which ethyl cellulose of various viscosities can be used. In addition, it is possible to include additional excipients, such as colorants, flavors, flavors, preservatives, antioxidants, solvents, blowing agents, lubricants, and mixtures of such substances.

Table 1 below shows various exemplary compositions of the two-layer cachet layers 3 of the present invention.

The lamellar, in particular film, foil or cachet preparation 3 containing the active pharmaceutical ingredient, contains at least one first layer 9a containing the active substance. Layer 9a containing the active substance preferably contains a polymer, more preferably a film-forming polymer, where the fraction of the polymer in the layer 9a containing the polymer and the active substance is from 10 to 90 wt.%, Preferably from 20 to 70 wt.% And more preferably from 30 to 60 wt.%, And where the layer containing the active substance, in particular, a two-layer cachet, is an adhesive layer 9a, and where the polymer is a water-soluble and / or water-degradable and / or water-degradable film-forming polymer.

In addition, a lamellar, in particular film, foil or cachet preparation 3 containing an active pharmaceutical ingredient, contains at least one active substance-free layer 9 c, which does not contain an active pharmaceutical ingredient. In the case of a three-layer cachet 3, it contains an additional active substance-free layer 9d, which also does not contain an active pharmaceutical ingredient. Such a first layer 9 c not containing an active substance and / or such an additional layer 9 d not containing an active substance is preferably a water-insoluble layer, for example made of or containing ethyl cellulose. The active substance-free layer 9 c and / or the active substance-free additional layer 9d can be formed as an adhesive layer, in particular in a two-layer wafer 3, in which the layer consists, for example, of hydroxypropyl methylcellulose or contains it. In a multilayer, in particular in a three-layer, wafer 3, the layer 9a containing the active substance is preferably located between two layers 9c, 9d not containing the active substance, where the layer 9a containing the active substance can be located between the first layer 9c, not containing an active substance and an additional layer 9d not containing an active substance, and preferably the first layer 9 c containing no active substance is a water-insoluble layer, which more preferably contains ethyl cellulose, and at least one n additional layer 9d, not containing active substance is an adhesive layer which preferably comprises a hydroxypropyl methylcellulose. Example 4 - Three-layer drug

The three-layer preparations, in particular cachets, of the present invention preferably comprise a mucoadhesive layer containing an active substance, a water-insoluble layer called a coating layer, and an adhesive protective layer. The mucoadhesive layer containing the active substance can be composed of mucoadhesive polymers such as cellulose derivatives, starch and starch derivatives, polyvinyl alcohol, polyethylene oxide, polyethylene, polypropylene, polyacrylic acid and polyacryl derivatives, polyvinylpyrrolidone, povidone, copovidone, copovidone gum, guar gum, carrageenan, pectins, dextrans, lectins, chitosan, pullulan, as well as mixtures of these substances; plasticizers, such as polyethylene glycol, glycerol, sorbitol, as well as mixtures of these substances; solvents such as water, ethanol, methanol, acetone, organic solvents, as well as mixtures of these substances. In addition, excipients such as colorants, flavors, flavors, preservatives, antioxidants, absorption enhancers, solvents, decomposition accelerators, lubricants and mixtures of such substances may be included. In particular, substances from the following groups are suitable as active pharmaceutical ingredients: drugs acting on the skeleton and muscles, drugs acting on the nervous system, hormones and drugs acting on the hormonal system, drugs that have a gynecological effect, drugs acting on the cardiovascular system, drugs acting on the respiratory system, drugs acting on the gastrointestinal - intestinal tract, diuretics, drugs acting on the sensory organs, cutaneous preparations, vitamins and minerals, peptide drugs and proteins, analgesics, anti-infective and antiparasitic drugs. The coating layer can be made of a layer of ethyl cellulose of various thicknesses, in which ethyl cellulose of various viscosities can be used. Moreover, it is possible to add other auxiliary substances, such as colorants, flavors, flavors, preservatives, antioxidants, solvents, blowing agents, lubricants and mixtures of such substances. The adhesive backing layer may vary in thickness and may be made of mucoadhesive polymers such as cellulose derivatives, starch and starch derivatives, polyvinyl alcohol, polyethylene oxide, polyethylene, polypropylene, polyacrylic acid and polyacryl derivatives, polyvinyl pyrrolidone, povidone alginine, copov , xanthan gum, guar gum, carrageenan, pectins, dextrans, lectins, chitosan, pullulan, as well as mixtures of these substances; a solvent such as water, ethanol, methanol, acetone, organic solvents, as well as mixtures of these substances. In addition, other auxiliary substances, such as colorants, flavors, flavors, preservatives, antioxidants, absorption enhancers, solvents, decomposition accelerators, blowing agents, lubricants and mixtures of such substances, may be included.

Table 2 below shows exemplary layer compositions of such a three-layer plate 3.

The lamellar preparation 3 of the pharmaceutical dosage form 1 of the present invention may also consist of one layer or several layers, in particular two.

Example 5

Regarding the calculation of the amount of active ingredient per cachet:

In particular, the amount of active ingredient based on the thickness of the wet polymer film layer can be calculated by the following formula:

wherein

m mass [g]

p density [g / cm ³ ]

A area [cm ² ]

h height [μm]

In this context, it is important to bear in mind that the height of the knife coating device is not equal to the thickness of the wet wafer layer. Examples of reasons for this include, for example, shear of the polymer film during its distribution, spreading or dripping of the polymer composition after distribution, and thickening of the polymer film at the edges. The extent of these processes depends, among other things, on the viscosity of the polymer solution and on the active pharmaceutical ingredient used. Thus, for each active pharmaceutical ingredient, a specific fraction can be added to the calculated amount of the active ingredient. Such an additional fraction is

- 35% for fluorescein sodium

- 40% for quinine

- 35% for diclofenac sodium

Moreover, you can use a specific factor of the drug to adjust the estimated amount, where, in particular, the specific factor of the drug is 100% + additional fraction, and thus the formula has the form:

Example 6 - Production of single-layer wafers:

The manufacture of single-layer wafers was carried out by a method of molding by dipping into a solution in which all the ingredients were first dissolved in a solvent, homogenized and then distributed over the appropriate release substrate to the desired thickness using a knife coating device. Then, the resulting film was dried under certain conditions and then cut into pieces of the appropriate size.

Further, the manufacturing methods of the preparations indicated in Example 2 above are described in detail:

And First, polyvinyl alcohol (PVA) was dissolved in demineralized water in a beaker at a temperature of 90 ° C and with a stirring speed of 400 rpm. Then, polyethylene glycol 400 (PEG 400) and a drug substance or drug solution, respectively, were added, and the solution was homogenized. At the end, hydroxypropylmethyl cellulose (HPMC) was added while stirring, homogenized and the losses due to evaporation by demineralized water were compensated. The polymer solution was covered and left overnight, and the next day was centrifuged at a speed of 4400 rpm for 50 min to remove air bubbles. Then, the solution was uniformly distributed over the release substrate using a knife coating device and the polymer film was dried for 6 hours at a temperature of 40 ° C in an oven. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. A single layer plate was stored on a release substrate and wrapped in aluminum foil.

B. First, polyvinyl alcohol (PVA) and Kollicoat ^® IR (kollikoat IR) were dissolved in demineralized water in a beaker at a temperature of 90 ° C and with a stirring speed of 400 rpm. Then, a drug substance or a solution of a drug substance was added, respectively, homogenized and compensated for the evaporation loss by demineralized water. The polymer solution was covered and left overnight, and the next day was centrifuged at a speed of 4400 rpm for 15 minutes to remove air bubbles. Then, the solution was uniformly distributed over the release substrate using a knife coating device, and the polymer film was dried for 5 hours at a temperature of 40 ° C. in an oven. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. A single layer plate was stored on a release substrate and wrapped in aluminum foil.

C First, polyvinyl alcohol (PVA) and IR collicoate were dissolved in demineralized water in a beaker at a temperature of 90 ° C and with a stirring speed of 400 rpm. Then, 85% glycerol and a drug substance or a solution of a drug substance were added, respectively, homogenized, and evaporation losses compensated by demineralized water. The polymer solution was covered and left overnight, and the next day was centrifuged at a speed of 4400 rpm for 15 minutes to remove air bubbles. Then, the solution was uniformly distributed over the release substrate using a knife coating device, and the polymer film was dried for 5 hours at a temperature of 40 ° C. in an oven. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. A single layer plate was stored on a release substrate and wrapped in aluminum foil.

Example 7 - Production of multilayer wafers

For the manufacture of multilayer wafers, such as those indicated in Example 3 and Example 4, first, individual layers were made by molding by dipping into a solution. Based on this, all the ingredients of the layer were dissolved in a solvent, homogenized and then distributed on the appropriate release substrate to the desired thickness using a knife coating device. Then, the individual layers were either distributed onto each other, or connected together in various ways, such as pressing or “bonding”. After that, the resulting film was cut into pieces of the appropriate size.

The following describes in detail the manufacturing methods of the above compositions of two- and three-layer wafers:

Production of two-layer wafers:

1. First, a polymer solution for the mucoadhesive layer containing the active substance was prepared in accordance with paragraph “Production of single-layer wafers A” and a 4% (vol.%) Solution of ethyl cellulose (EC solution) in acetone was prepared. Then, the EC solution was uniformly applied to the release substrate to the desired thickness and dried at room temperature for 15 minutes. Then, the polymer solution was evenly distributed using a knife coating device and the resulting film was dried at 40 ° C for 6 hours in an oven. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. The two-layer wafer was stored on a release substrate and wrapped in aluminum foil.

2. First, in accordance with the paragraph “Production of single-layer plates A”, a polymer solution was prepared for the mucoadhesive layer containing the active substance and a 4% (vol.%) Solution of EC in acetone. Then, the EC solution was uniformly distributed over the release substrate using a knife coating device and the polymer film was dried for 4 hours at a temperature of 40 ° C in an oven. Then, the EC solution was uniformly applied to the partially dried, still viscous polymer film with a layer of the desired thickness. In the end, the resulting two-layer film was again dried for 2 hours at a temperature of 40 ° C in an oven, as a result of which both layers were firmly connected. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. The two-layer wafer was stored on a release substrate and wrapped in aluminum foil.

3. First, in accordance with the paragraph "Production of single-layer plates A", a polymer solution was prepared for a mucoadhesive layer containing the active substance and a 4% (vol.%) Solution of EC in acetone. Then, the polymer solution was uniformly distributed over the release substrate using a knife coating device, and the polymer film was dried for 4 hours at a temperature of 40 ° C. in an oven. At the same time, the EC solution was uniformly applied to the second releasing substrate with a layer of the desired thickness and dried for 15 minutes at room temperature. Then, the resulting EC film was carefully removed from the release substrate and pressed into a partially dried, still viscous polymer film using a roller. In the end, the two-layer film was dried for 2 hours at a temperature of 40 ° C in an oven, as a result of which both layers were firmly connected. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. The two-layer wafer was stored on a release substrate and wrapped in aluminum foil.

Production of three-layer wafers:

1. First, in accordance with the paragraph "Production of single-layer plates A", a polymer solution was prepared for a mucoadhesive layer containing the active substance, a 4% (vol%) solution of EC in acetone and 0.5% (vol.%) HPMC in cold, demineralized water . Then, the EC solution was uniformly applied to the release substrate to the desired thickness and dried at room temperature for 15 minutes. Then, the polymer solution was evenly distributed using a knife coating device and the resulting film was dried at 40 ° C for 6 hours in an oven. At the end, the HPMC solution was distributed onto a two-layer film as a third layer using a knife coating device and dried again for 2 hours at a temperature of 40 ° C in an oven, as a result of which both layers were firmly connected. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. The three-layer wafer was stored on a release substrate and wrapped in aluminum foil.

2. First, in accordance with the item “Production of single-layer plates A”, a polymer solution was prepared for the mucoadhesive layer containing the active ingredient, a 4% (vol%) solution of EC in acetone and 0.5% (vol.%) HPMC in cold, demineralized water . Then, the EC solution was uniformly applied to the release substrate to the desired thickness and dried at room temperature for 15 minutes. Then, the polymer solution was evenly distributed using a knife coating device, and the resulting film was dried for 6 hours at a temperature of 40 ° C in an oven. At the same time, the HPMC solution was evenly distributed on the second releasing substrate with a layer of the desired thickness and dried for 2 hours at a temperature of 40 ° C in an oven. Then the HPMC film was carefully removed from the release plate and glued onto a two-layer film using water as a binder. In the end, the resulting two-layer film was dried for 1 h at a temperature of 40 ° C in an oven, as a result of which all layers were firmly connected. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. The three-layer wafer was stored on a release substrate and wrapped in aluminum foil.

3. First, in accordance with the paragraph "Production of single-layer plates A", a polymer solution was prepared for the mucoadhesive layer containing the active ingredient, a 4% (vol%) solution of EC in acetone and 0.5% (vol.%) HPMC in cold, demineralized water . Then, the solution was uniformly distributed over the release substrate using a knife coating device and the polymer film was dried for 6 hours at a temperature of 40 ° C in an oven. At the same time, the HPMC solution was evenly distributed over the second releasing substrate with a layer of the desired thickness and dried for 1 h at a temperature of 40 ° C in an oven. Then, the resulting polymer film was carefully detached from the release substrate and pressed into a partially dried, still viscous HPMC film using a roller. Then, the two-layer film was dried for 1 h at a temperature of 40 ° C in an oven, as a result of which both layers were firmly connected. Then, the EC solution was uniformly applied to the two-layer film using a knife coating device, and the resulting three-layer film was dried for 30 minutes. at room temperature. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. The three-layer wafer was stored on a release substrate and wrapped in aluminum foil.

4. First, in accordance with the item “Production of single-layer plates A”, a polymer solution was prepared for the mucoadhesive layer containing the active ingredient, a 4% (vol%) solution of EC in acetone and 0.5% (vol.%) HPMC in cold, demineralized water . Then, the EC solution was uniformly distributed over the release substrate to the desired thickness and dried for 2 hours at a temperature of 40 ° C in an oven. Then, the polymer solution was distributed using a knife coating device, and the resulting two-layer film was dried for 4 hours at a temperature of 40 ° C in an oven. At the same time, the EC solution was uniformly applied to the second releasing substrate with a layer of the desired thickness and dried for 15 minutes at room temperature. Next, the resulting EC film was carefully disconnected from the release substrate and pressed into a partially dried, still viscous, two-layer polymer film using a roller. At the end, the three-layer film was dried for 2 hours at 40 ° C in an oven, so that both layers were firmly connected. Before testing and subsequent use, the film was cut into pieces of the appropriate size and disconnected from the release substrate. The three-layer wafer was stored on a release substrate and wrapped in aluminum foil.

The features of the present invention disclosed in the description above, in the claims, as well as in the drawings, may be significant, individually or in any combination, for the implementation of the invention in its various embodiments.

In FIG. 8a is a schematic illustration of a pharmaceutical dosage form 1 of the present invention in accordance with a fourth embodiment of the present invention. In particular, this image shows a pharmaceutical dosage form 1 in which the plate preparation 3 is in a compact form. Moreover, without limiting the scope of this example, in FIG. 8a shows a side view of the pharmaceutical dosage form 1. A portion of the plate preparation 3 is rotated around the rod 19. This roll of the plate preparation 3 and the rod 19 together with the extended portion of the plate preparation forms a release mechanism. It should be understood that in some embodiments of the fourth embodiment, the release mechanism 4 does not require a rod 19, therefore, it is absent. Shell 2 comprises a release mechanism 4 in the interior 7 of the shell 2. Thus, the plate preparation 3 and the shape of the release mechanism are protected. Preferably, the shell 2 is capsule shaped. Such a capsule 2 helps to swallow a dosage form, or in particular a portion of a dosage form, which must be swallowed to achieve the desired use. Moreover, the shell 2 contains an opening 6 through which the plate preparation 3 can leave the shell 2. It should be understood that the hole 6 can also be considered part of the release mechanism 4, since it promotes the release of the plate preparation 3. The trigger mechanism 5 is connected to the preparation 3 and is located outside the shell 2. It should be understood that part of the trigger mechanism 5 may be located inside the shell 2, and / or part of the plate preparation 3 may be located outside the shell 2. Moreover, the trigger mechanism 5 may be formed as a complex part of the plate preparation 3. Additionally, the shell 2 contains a sealed layer that seals the hole 6 in at least the initial state of dosage form 1, in particular in the state of dosage form 1, which is suitable for storage. Thus, the interior of the casing 7 can be protected from environmental factors such as humidity, liquids, or microorganisms.

In particular, the fourth embodiment relates to an oral dosage form for treating the mucous membrane of the esophagus. In this case, it can deliver beneficial substances, such as the active pharmaceutical ingredient, to the mucous membrane of the esophagus by spinning the plate preparation 3 when moving along the esophagus when the dosage form is swallowed. Thus, the active pharmaceutical ingredients that the laminar preparation 3 contains can be released topically on the mucous membrane of the esophagus. Existing methods of treating local diseases of the esophagus, as a rule, use swallowing the contents of application systems that were developed for inhalation therapy of the lungs, or swallowing a gel containing specific active substances. However, as a rule, the swallowed contents of the application systems or gel have a short contact time with the mucous membrane of the esophagus. Thus, local and systemic effects can be enhanced, in particular, compared with the form of application in which the contact time is prolonged. By applying the plate preparation 3 on the mucous membrane of the esophagus in the case of the pharmaceutical dosage form 1 of the present invention in accordance with the fourth embodiment of the present invention, the treatment of local diseases of the esophagus can be improved, and in particular, the contact time can be prolonged. When applied to the mucous membrane of the esophagus, the lamellar preparation 3 continues to contact the mucous membrane, and also provides a controlled release of the active pharmaceutical ingredient for local treatment or diagnosis. Preferably, the controlled release cannot be immediate, delayed or prolonged, it is also preferable that, during or after the release of the active pharmaceutical ingredient or active pharmaceutical ingredients, the plate preparation 3 is dissolved and preferably swallowed. Moreover, the shell 2 may be detached from the plate preparation 3 immediately after the release of the plate preparation 3 or may dissolve while still attached to the flat preparation 3. Preferably, the shell 2 is made of soluble and / or digestible material. Moreover, the trigger mechanism 5 is a holding device. In particular, the holding device may be configured to lock it in the oral cavity. Based on this, the holding device 5 has a mucoadhesive surface, preferably containing cellulose derivatives, starch and starch derivatives, polyvinyl alcohol, polyethylene oxide, polyethylene, polypropylene, polyacrylic acid and polyacrylate derivatives, polyvinylpyrrolidone, povidone, copovidone, sodium alginate, guar gum, carrageenan, pectins, dextrans, lectins, chitosan, pullulan and mixtures of such substances. Thus, the holding device 5 can be attached to the mucous membrane of the oral cavity, in particular to the mucous membrane of the cheek, i.e. to the inside of the cheek.

More specifically, a fourth embodiment of the present invention may relate to a pharmaceutical dosage form for the treatment of eosinophilic esophagitis. Eosinophilic esophagitis is an inflammatory, immuno-mediated disease with increased relevance of disorders of the gastrointestinal tract. The treatment of this disease can be carried out using topical steroids. Preferably, the shell 2 is a capsule made of hard gelatin. In the initial state of dosage form 1, the plate preparation 3 has a compact shape, in particular a spiral shape, which is attached to the trigger mechanism 5. The trigger mechanism 5 is a holding device, as described above. With the introduction of the holding device is attached in the oral cavity, preferably to the mucous membrane of the cheek, in particular, due to adhesion to the mucous membrane. Further, dosage form 1 is swallowed, preferably with a drink or water, whereby dosage form 1 moves along the esophagus, and a force acting on the holding device 5 triggers the release of the plate preparation 3 by the release mechanism 4. When the dosage form 1 moves along the esophagus, the plate preparation 3 is untwisted and thus released. Preferably, the platelet preparation is mucoadhesive, whereby it may adhere to the mucosa of the esophagus. In this case, the contact and / or position of the plate preparation is independent or depends not only on the holding device 5. Subsequently, the elongated portion of the mucous membrane of the esophagus is covered with the preparation 3 or at least approaches it. Thus, the mucous membrane of the esophagus can be treated with active pharmaceutical ingredients, in particular topical steroids released by drug 3. Preferably, the lamellar preparation can contain and release fluticasone or budesonide.

Preferably, the lamellar preparation 3, in particular in accordance with the fourth embodiment of the present invention, is made by dipping in a solution, where all the ingredients are first dissolved in a solvent, homogenized and then distributed onto a stable releasing substrate with a layer of the desired thickness using a knife coating device. Then, the resulting film was dried under certain conditions and then cut into pieces of the appropriate size.

In a preferred embodiment, the ingredients, in particular the polymer matrix, consists of 10% w / w. a solution of polyvinyl alcohol (PVA) (moviol 40-88) in 20% wt./mass. aqueous solution of collicoate IR.

In addition, an active pharmaceutical ingredient, such as fluticasone or budesonide, as well as excipients, such as methylene blue, are added as a visual control.

A plate preparation 3 made in accordance with the present preferred embodiment was experimentally analyzed. To this end, the plate preparation 3 was tested for film thickness and mass uniformity. Moreover, the complete decay time was tested both on purified water and on a moistened alginant gel (3% w / w) to simulate the mucous membrane. Total decay was defined as the absence of any solid matrix particles. Tensile strength, elongation and extraction force were measured using a texture analyzer. All tests were performed three times, the report sets out the average positive / negative standard values. The resulting plate preparation 3 has a thickness of 114 ± 5 μm and an average weight of 9.39 ± 0.03 mg / cm ² . The total decay time in water was 760 ± 35 s and more than 1200 s in an alginant gel. The tensile strength was 31.35 MPa. The elongation at break was 7.41 ± 0.90%. Preferably, the pharmaceutical dosage form 1, in particular in accordance with the fourth embodiment of the present invention, can be manufactured in accordance with the following description:

- cutting the film obtained by dipping into a solution into strips of 400 mm by 4 mm;

- folding or twisting of the resulting plate preparation 3;

- providing a hard gelatin capsule of size 1, which is a shell 2;

- cutting holes 6 in one of the parts of the hard gelatin capsule 2, namely, as shown in the image, in the upper part;

- pulling one end of the plate preparation 3 through the hole 6; and

- closure of the capsule 2.

In this case, the trigger mechanism, in particular the holding device 5, is formed by the part of the plate preparation 3, which is located outside the shell 2, and the release mechanism 4 is formed by the part of the plate preparation 3, which is located inside the shell 2, and preferably the hole 6.

Dosage form 1, made as described above, containing a preferred embodiment of the plate preparation 3, in particular in the case of the fourth embodiment of the present invention, was experimentally analyzed as described above. The extraction force of the plate preparation 3 from the capsule 2 was 0.31 ± 0.09 N in the case of a twisted plate preparation 3 and 0.24 ± 0.45 N in the case of a folded plate preparation 3.

In FIG. 8b is a schematic illustration of a pharmaceutical dosage form 1 of the present invention in accordance with a fourth embodiment of the present invention. In particular, this image shows a pharmaceutical dosage form 1, in which the plate preparation 3 is at least partially in expanded form. Moreover, without limiting the scope of this example, FIG. 8b shows a top view of the pharmaceutical dosage form 1. Shell 2 comprises a rod 19 and a portion of the plate preparation 3, which is still twisted or folded, which forms the release mechanism 4. The plate preparation 3 exits the shell 2 through the opening 6. In particular, it unwinds the shell 2, i.e. in the inner space 7 of the shell, and then extends in the direction of the hole 6.

In addition, the plate preparation 3 is divided into two sections, the first section of the plate preparation Over and the second section of the plate preparation 3b. The first section B and the second section 3b may contain various active pharmaceutical ingredients. Preferably, the first portion 3a may contain local anesthetics such as benzocaine, butamben, dibucaine, lidocaine, oxybuprocaine or novocaine, and the second portion 3b may contain steroids such as corticosteroids, glucocorticosteroids, fluticasone, budesonide or clocortolone. In particular, in this case, in the treatment of the esophagus, the vomiting reflex can be suppressed by local anesthetics, and the mucous membrane of the esophagus can be treated with steroids. Additionally, the first portion 3a has a smaller cross-sectional area than the second portion 3b. In particular, it successfully contributes to the swallowing of the dosage form.

In addition, the retaining device 5 is attached to the preparation 3 or is an expanded part of the plate preparation 3 with a mucoadhesive layer, preferably comprising: mucoadhesive polymers such as cellulose derivatives, starch and starch derivatives, sodium alginate, gelatin, xanthan gum, guar gum, carrageenan, carrageenan , pectins, dextrans, lectins and mixtures of such substances.

Additionally, the trajectory of the movement of the PM dosage form 1.

Preferably, formulation 3 is made in accordance with one of the manufacturing procedures described herein. In particular, a plate preparation having several sections, especially at least the first section 3a and at least the second section 3b, can be made similarly to a multilayer preparation in which the layers of at least some of the layers are offset relative to each other, but all still partially overlap. Also in this way, a holding device 5 can be manufactured and / or attached to the preparation 3.

In FIG. 8c shows envelope cross-sectional surfaces of a fourth embodiment of the present invention.

The pharmaceutical dosage form 1, in particular, shell 2, and the plate preparation 3, in particular, a portion of the plate preparation 3, which has already been released, for example, a portion from section 3b, are shown as they look when viewed in the direction of the motion path. Thus, the motion path in FIG. 8c points to the drawing area. As shown, the envelope surface of the cross section of the dosage form AD is larger than the envelope surface of the cross section of the released portion of the plate preparation AR. In particular, this facilitates the ingestion of an orally administered pharmaceutical dosage form 1.

FIG. 8a, b, and c have the same scale. It should be understood that the plate preparation 3 may be wider or narrower relative to the capsule 2 than shown. Preferably, the lamellar preparation may be wider in order to better utilize the inner space 7 of the shell. Alternatively, the plate preparation may be twisted, with some turns of the plate preparation 3 being biased relative to each other. Thus, in particular, the inner space 7 is used more efficiently. Also preferably, the plate preparation 3 may form or may enter a sectional element that is twisted or folded. In particular, such a sectional element can be folded in an efficient, reliable and / or compact manner.

Notation list

1 pharmaceutical dosage form

2 shell

3 plate preparation

3a, 3b sections of the plate preparation, in particular, the first and second section

4 release mechanism

5 trigger mechanism

6 hole

7 shell interior

8 predefined break point

9 layer

9a, 9b layer containing the active substance

9c, 9d layer containing no active substance

10 spring element

11 first tubular element

12 additional tubular element

13 first connecting element

14 additional connecting element

15 center plate cylinder hole

16 slot

17 elements of the coating or shell

18 sealing coating

19 rod

PM motion path

AD envelope cross-sectional surface of the dosage form

AR envelope surface of the cross section of the released portion of the plate preparation

Claims (38)

1. A pharmaceutical dosage form for use on the mucous membrane of the esophagus, nasopharynx, buccal, gastrointestinal, rectal or vaginal mucosa, which contains at least: one lamellar preparation containing an active pharmaceutical ingredient, release mechanism and a trigger mechanism configured to trigger release by the release mechanism of the plate preparation at a predetermined site of exposure to the gastrointestinal tract, rectum or vagina, and the pharmaceutical dosage form contains a shell containing the specified plate product containing the active pharmaceutical ingredient, and the shell has at least one hole through which the liquid surrounding the shell can come into contact with the interior of the shell, where the hole is made in the form the slots and / or at least partially covered by a trigger mechanism, or the lamellar preparation is folded into grooves or recesses of the dosage form, the folds being glued together with a polymer, which triggers the release of the pharmaceutical ingredient; and moreover, the release mechanism is an expansion mechanism selected from the group consisting of a mechanical expansion system, a gas expansion system, compressed foam or compressed fabric, and the expansion of the expansion mechanism leads to the opening of the shell; or the hole forms part of the release mechanism and is configured to release the drug from the membrane so that the plate preparation unwinds or straightens as the dosage form advances along the mucous membrane of the esophagus and exits the membrane through the hole. 2. The pharmaceutical dosage form according to claim 1, in which: the trigger mechanism is configured to trigger the release of the plate preparation using the release mechanism after contacting the pharmaceutical dosage form with a key stimulus, and / or the trigger mechanism is configured to trigger the release of the plate preparation using the release mechanism in a time-controlled manner or immediately, and / or the release mechanism is configured to release the plate preparation in a time-controlled manner or immediately after the trigger mechanism is started. 3. The pharmaceutical dosage form according to claim 1, which contains the drug in folded form, and the expansion of the expansion mechanism leads to the straightening of the drug. 4. The pharmaceutical dosage form of claim 1, wherein the shell comprises, as a release mechanism and as an expansion mechanism, a gas-generating substance that is in that part of the shell that is opposite to the part of the shell containing the drug, or in which the shell and mechanical expansion system contain at least a first connecting or lever element, and / or in which the shell and the mechanical expansion system comprise at least one spring element, or in which the shell at least contains a first tubular element and an additional tubular element, where the second tubular element has a smaller tube diameter than the first tubular element, and is located at least partially in the first tubular element, and the shell further comprises a spring element which is positioned so that it can move said at least one second tubular element in the longitudinal direction relative to the first tubular element, or in which the shell, in particular the expansion mechanism, contains at least a connecting or lever element, and in which the shell and the mechanical expansion system contain at least an additional connecting or lever element, the first connecting or lever element and / or additional a connecting or lever element is located at the free end of the shell. 5. The pharmaceutical dosage form according to any one of the preceding paragraphs, in which the preparation contains a substance that promotes swelling, which is selected from the group consisting of sponges and fibers. 6. The pharmaceutical dosage form according to claim 4, in which the first connecting or lever element and / or additional connecting or lever element, at least partially covered by a trigger mechanism, and / or in which at least one first connecting or lever element or at least one additional connecting or lever element is located so that the connecting or lever element at one end is directly adjacent to the corresponding connecting or lever element, laid on the other end. 7. The pharmaceutical dosage form according to any one of the preceding paragraphs, in which: the lamellar preparation provides, after its release by the release mechanism, a relatively large surface area and comes into contact with a relatively large surface area; and / or the release mechanism is configured to release, at least in part, the lamellar preparation when moving along the mucous membrane. 8. The pharmaceutical dosage form according to any one of paragraphs. 1-3 or 7, in which: the release mechanism comprises a sectional element; the sectional element, after activating the release mechanism, can be expanded from a compact form, namely from a folded, compressed, twisted or rolled form, to an expanded form, namely to a straightened, common, open, elongated, stretched, untwisted or elongated shape; and the sectional element comprises, at least in compact form, a plate preparation, or in which the release mechanism is an expansion mechanism and an extension mechanism configured to straighten, stretch, unwind, roll or unwind the plate preparation due to leverage from external movement, force or pressure. 9. The pharmaceutical dosage form according to any one of paragraphs. 1-3, 7 or 8, in which the trigger mechanism is a holding device that is part of a plate preparation or attached to it. 10. The pharmaceutical dosage form according to claim 9, intended for oral administration, in which the trigger mechanism and the holding device are made with the possibility of fixation in the oral cavity and / or with the possibility of holding in the hand during administration of the pharmaceutical dosage form. 11. The pharmaceutical dosage form according to any one of the preceding paragraphs, intended for oral administration, in which at least during the release of the plate preparation, the released portion of the plate preparation and the dosage form move relative to each other, defining a trajectory (PM) of the dosage form and the envelope surface the cross section (AD) of the dosage form, visible in the direction of movement, is larger than the envelope surface of the cross section (AR) of the released portion of the plate th preparation. 12. The pharmaceutical dosage form according to claim 1, in which the plate preparation is a film, foil or cachet preparation. 13. The pharmaceutical dosage form according to claim 2, wherein said opening is at least partially coated with a trigger mechanism in the form of a soluble polymer that is capable of triggering the release of the plate preparation by the release mechanism after the trigger mechanism contacts the key stimulus. 14. The pharmaceutical dosage form according to claim 4, in which the trigger mechanism is formed by a soluble polymer located inside the tubular elements. 15. The pharmaceutical dosage form of claim 13, wherein the key stimulus is gastric juice or small intestinal fluid. 16. The pharmaceutical dosage form according to claim 1, in which in the initial state of the dosage form, the lamellar preparation has a compact form. 17. The pharmaceutical dosage form according to claim 1, wherein the release mechanism is formed by a portion of the plate preparation within the shell and orifice. 18. The pharmaceutical dosage form according to claim 8, in which the shell contains a rod, and part of the plate preparation is twisted or wrapped around the rod and together with the elongated part of the plate preparation forms a release mechanism. 19. The pharmaceutical dosage form according to claim 9, in which the retaining device is attached in the oral cavity by gluing to the mucous membrane. 20. The pharmaceutical dosage form according to claim 9, in which the holding device is connected to a plate preparation or is an expanded part of a plate preparation containing mucoadhesive polymers.

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